Protective effects and mechanism of Dachengqi decoction on intestinal septic mice / 中国药房

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

Dachengqi decoction reduces inflammatory response and promotes recovery of gastrointestinal function in patients with mild acute pancreatitis by regulating the intestinal microbiota / 中华危重病急救医学

Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

Observation and analysis on clinical efficacy of Dachengqi decoction for acute pancreatitis / 中华危重病急救医学

Objective:To observe the clinical efficacy of Dachengqi decoction combined with octreotide in the treatment of patients with acute pancreatitis (AP).Methods:From March 2018 to February 2021, a total of 68 patients with mild acute pancreatitis (MAP) and moderately severe acute pancreatitis (MSAP) admitted to Shanghai Traditional Chinese Medicine-Integrated Hospital were included, and they were randomly divided into western medicine treatment group and Dachengqi decoction group. The patients in the western medicine treatment group received conventional western medicine (octreotide+symptomatic treatment); in the Dachengqi decoction group, 100 mL of Dachengqi decoction was taken orally on the basis of conventional western medicine, twice a day; the observation time for both groups was 7 days. The levels of inflammation parameters [white blood cell count (WBC), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP)] and serum amylase (Amy) before and after treatment of patients between the two groups, as well as the occurrence of clinical efficacy indicators and adverse reactions were compared.Results:Among the 68 included patients, 4 were excluded because the specimen was not obtained or the patient gave up the treatment. A total of 64 patients were finally enrolled in the analysis, including 32 cases in the Dachengqi decoction group and 32 cases in the western medicine treatment group respectively. There was no statistically significant difference in inflammation parameters or serum Amy levels before treatment between the two groups. At 7 days of treatment, the inflammatory parameters and serum Amy levels of the two groups were significantly lower than those before treatment [western medicine treatment group: WBC (×10 9/L) was 5.94±2.08 vs. 11.81±3.66, IL-6 (ng/L) was 7.22 (5.72, 14.23) vs. 30.13 (15.77, 85.37), PCT (μg/L) was 0.068 (0.052, 0.128) vs. 0.290 (0.231, 0.428), CRP (mg/L) was 26.0 (18.3, 35.8) vs. 112.0 (62.0, 126.0), Amy (U/L) was 77 (57, 116) vs. 352 (162, 1 576); Dachengqi decoction group: WBC (×10 9/L) was 5.56±2.04 vs. 12.22±2.85, IL-6 (ng/L) was 5.70 (3.26, 11.06) was 50.30 (23.99, 88.32), PCT (μg/L) was 0.038 (0.028, 0.808) vs. 0.308 (0.129, 0.462), CRP (mg/L) was 11.0 (3.5, 24.0) vs. 150.0 (75.0. 193.0), Amy (U/L) was 78 (57, 104) vs. 447 (336, 718); all P < 0.05], and the levels of IL-6, PCT, and CRP decreased more significantly after treatment in the Dachengqi decoction group (all P < 0.05). The total clinical effective rate of patients in the Dachengqi decoction group was significantly higher than that of the western medicine treatment group [93.75% (30/32) vs. 71.88% (23/32), P < 0.05]. There was no obvious adverse event during the treatment and observation period in the two groups. Conclusion:Dachengqi decoction combined with octreotide therapy could improve the clinical efficacy of AP patients, and its mechanism might be related to reducing the level of inflammatory factors, thereby inhibiting the inflammatory response, and regulating the level of serum Amy.

Mechanism of lung and intestine combination therapy in treatment of acute lung injury by inhibiting inflammatory response based on NF-κB/NLRP3 signaling pathway and alveolar macrophage activation / 中国中药杂志

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.

Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology / 中国中药杂志

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1β(IL-1β), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

Analysis on syndrome differentiation and treatment of "heat fecaloma with watery discharge" in critically ill elderly patients / 中国中西医结合急救杂志

Objective In critically ill elderly patients with "heat fecaloma with watery discharge", deficiency syndrome occupies its eighty to ninety percent, while "heat accumulation" occupies its ten to twenty percent; in fact, it is "dry feces accumulation stagnation and manure water side stream". Factors of Qi deficiency, blood deficiency, Yin deficiency, Yang deficiency, etc. are the main causes of dry stool accumulating in the intestine and manure water flows to side stream. The therapeutic principles of this disease should be removing stasis by purgation, in the mean time supplementing Qi and moistening intestine, or moisturizing dryness by nourishing blood, or supplementing Yin and increasing fluids, or warming yang for relaxing bowels in order to solve the root causes of the disease. The mechanism of heat fecaloma with watery discharge in critically ill elderly patients is different from that of general patients; clinically it is necessary to interrogate the disease history in detail, synthesize the four diagnostic methods, and differentiate manifestations from root cause, deficiency from sthenia, mildness from severity and amelioration from urgency. Casually using attack should be avoided, and aiming to treat its root cause is the proper therapeutic method.

The effect of Dachengqi decoction combined withβ-aescine on pulmonary function in patients with acute lung injury after chest trauma / 中国中西医结合急救杂志

Objective To observe the effect of Dachengqi decoction combined with β-aescine on pulmonary function in patients with acute lung injury (ALI) after chest trauma.Methods Ninety-five patients with ALI after chest trauma admitted to the Department of Thoracic Cardiothoracic Surgery of Dingxi People's Hospital of Gansu from April 2013 to May 2016 were enrolled, and they were divided into a Dachengqi decoction group (47 patients) and a control group (48 patients) by random number table. The control group patients were treated with conventional therapy and β-aescine 0.4 mg/kg+ 10% Glucose (250 mL) intravenous drip, while the Dachengqi decoction group patients were additionally treated with Dachengqi decoction on the treatment of the control group (rhubarb 12 g, magnolia officinalis 24 g, fructus aurantii immaturus 12 g, mirabilite 9 g), one dose daily, taken twice in a day, once in the morning and once in the evening orally, both groups were treated for one week. Before and after treatment, the changes of esophageal pressure, respiratory dynamics, the indexes of pulmonary function and blood gas analysis were observed. Results Compared with those before treatment, the levels of plateau pressure (Pplat), mean airway pressure (mPaw), airway resistance (Raw) and arterial partial pressure of carbon dioxide (PaCO2) of the two groups after treatment were significantly reduced, but the levels of lower esophageal sphincter pressure (LESP), peak airway pressure (PIP), the first second forced expiratory volume (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEF), the mean maximum expiratory flow (MMEF), pulse oxygen saturation (SpO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2) were all increased significantly; the changes of the above indexes in the Dachengqi decoction group were more significant than those in the control group [LESP (mmHg, 1 mmHg = 0.133 kPa):18.64±2.79 vs. 15.46±3.09, Pplat (cmH2O, 1 cmH2O = 0.098 kPa): 14.27±1.68 vs. 16.00±1.87, PIP (cmH2O): 40.23±5.03 vs. 32.19±4.45, mPaw (cmH2O): 8.57±0.67 vs. 9.41±1.23, Raw (cmH2O·L-1·s-1): 6.76±1.01 vs. 9.31±1.43, FEV1 (L): 1.73±0.27 vs. 1.46±0.25, FVC: (3.95±0.51)% vs. (3.30±0.46)%, PEF (L/s): 3.81±0.47 vs. 3.11±0.38, MMEF (L/s): 0.93±0.16 vs. 0.77±0.12, SpO2: 0.96±0.06 vs. 0.91±0.05, PaO2 (mmHg): 97.82±10.13 vs. 74.73±8.02, PaCO2 (mmHg): 36.49±4.28 vs. 47.13±5.46, PaO2/FiO2 (mmHg): 362.47±20.82 vs. 259.79±17.61, allP < 0.05]. Conclusion Dachengqi decoction combined with β-aescine can reduce the respiratory intensity of patients with ALI after chest trauma and improve the lung function and blood oxygen level.

Effect of Dachengqi decoction, omeprazole and cisapride in the treatment of gastric cancer radical operation in serum gastrin and motilin / 中国生化药物杂志

Objective To evaluate the effect of Dachengqi decoction,omeprazole and cisapride in the treatment of gastric cancer radical operation in serum gastrin and motilin.Methods 88 cases of gastric cancer after radical gastrectomy from May 2013 to July 2015 in our hospital were selected and divided into control group and treatment group with each 44 cases.Patients in both groups were given routine treatment and symptomatic treatment.Control group received omeprazole Enteric-coated capsules 20mg,qd,cisapride tablets 10mg,tid,treatment group received more Dachengqi decoction 200mL,bid,respectively by intragastric injection and retention enema,two times a day,a total of 21 days of treatment.The clinical efficacy,serumgastrin,plasma gastric motility,gastric juice volume and adverse reactions were compared between the two groups.Results The total effective rate in the treatment group was significantly higher than that in control group(P<0.05); After treatment,gastric juice volume of two groups was significantly lower than before treatment,the gastric juice volume in the treatment group were significantly lower than control group(P<0.05);Compare with pre-treatment,after treatment,the serum gastrin,plasma gastric motility levels of two groups were significantly higher,and the treatment group were significantly higher than the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Omeprazole,cisapride combined with Dachengqi decoction in the treatment of gastric cancer radical operation was obvious and high safety.

Effects of Dachengqi Decoction on Pulmonary Histology and Total IgE Levels in Mice with Allergic Asthma / 中国中医药信息杂志

Objective To explore the effects ofDachengqiDecoction on morphological changes, lung and spleen indexes, and total IgE levels of mice with allergic asthma; To discuss it relevant mechanism of action.MethodsThe method of OVA sensitization and provocation was used to establish allergic asthma mice models. 20 C57BL/6 mice were randomly divided into control group, model group,Dachengqi Decoction group and dexamethasone positive group. Each medication group was given relevant medicine for gavage. Lung and spleen indexes in each group were detected. The total IgE levels in serum of mice were detected by ELISA, and HE staining was used to conduct pathological observation.Results Compared with control group, the lung index and level of IgE in model group increased significantly and pulmonary histological results showed abundant inflammatory cells infiltrated in the bronchus; compared with the model group, the lung index as well as the levels of IgE decreased significantly in the Dachengqi Decoction and dexamethasone positive group (P<0.05), and the lung tissue organization form was improved significantly.ConclusionDachengqi Decoction has inhibiting effects on pulmonary inflammation of mice with asthma.

In vivo pharmacokinetic study on several active components of Dachengqi Decoction in rats by UPLC-MS/MS / 中草药

Objective: To study the in vivo pharmacokinetics of aloe emodin, rhein, emodin, chrysophanol, physcion, hesperidin, neohesperidin, naringin, honokiol, and magnolol in plasma of rats after ig administration of Dachengqi Decoction. Methods: After ig administration of Dachengqi Decoction (10.35 g/kg), the blood was collected from the retinal vein plexus of rats at predetermined time and pre-prepared with 1,8-dihydroxyanthraquinone as internal standard (IS). A reliable ESI source, negative ion mode scanning, and multiple reaction monitoring (MRM) method were developed for the simultaneous determination of the active components in Dachengqi Decoction and chromatography was carried out on a Shimadzu Shim-pack XR-ODS III (75 mm × 2.0 mm, 1.6 μm) using a gradient mobile phase consisted of methanol and 0.1% formic acid water at a flow rate of 0.35 mL/min. Calculations of the pharmacokinetic data were performed using WinNonlin 4.1 software. Results: Calibration curves for aloe emodin, rhein, emodin, chrysophanol, physcion, hesperidin, neohesperidin, naringin, honokiol, and magnolol in plasma of rats were linear within the ranges of 0.52—520.00, 2.06—616.00, 0.57—568.00, 3.1—1 240.0, 18.5—1 000.0, 1.94—972.00, 1.59—796.00, 1.63—816.00, 0.025—50.000, and 0.027—53.300 ng/mL, respectively. The precision, recovery, and stability of each component in the present assay were acceptable for the analysis. They are in the line with the requirements of biological sample analysis. The concentration of physcion in plasma of rats was under the limit of detection at almost every time point, thus we failed to obtain the pharmacokinetic parameters of it. While the plasma concentration and pharmacokinetic parameters of other components were successfully calculated. Conclusion: The proposed method can be used for the simultaneous determination of the concentration of several active components in plasma of rats and successfully applied to the pharmacokinetic study of the analytes in rats after ig administration of Dachengqi Decoction.

Mitigation of the damage of intestinal smooth muscle of rats with multiple organ dysfunction syndrome by Dachengqi decoction through mitochondrial pathway / 中华危重病急救医学

ObjectiveTo discuss the mechanism of promotion of gastrointestinal motility during multiple organ dysfunction syndrome ( MODS ) by Dachengqi decoction, by examining the expression of Bcl-2, Bax of mitochondrial pathway, and nuclear factor-κB (NF-κB) in smooth muscle of the small intestinal in rats.Methods According to the random number table, 100 healthy adult Wistar rats were divided into three groups: control group with 20 rats, model group with 40 rats, and Dachengqi decoction group with 40 rats. Rat model of MODS was reproduced by bacterial peritonitis induced by an injection of 1 mLEscherichia coli suspension (8×108 cfu/mL) into peritoneal cavity. The rats in control group were given 1 mL normal saline intraperitoneally. The rats in Dachengqi decoction group were given 10 mL/kg Dachengqi decoction by gavage, twice a day, before inoculation of the bacterial suspension. Twenty-four hours after modelling, rats in all groups were sacrificed by cervical vertebra luxation, and the upper small intestine was harvested to detect the protein expressions of Bcl-2, Bax, and NF-κB in smooth muscle tissue using immunohistochemical staining.Results In the control group, a large amount of Bcl-2 protein was expressed and it was distributed uniformly in small intestinal smooth muscle. On the other hand, a small amount of Bax and NF-κB protein was expressed, and they were also distributed uniformly. Compared with the control group, Bcl-2 protein was distributed only sparsely, and it was scattered in intestinal smooth muscle in blocks in the model group. The expression of Bcl-2 protein was obviously down-regulated [integral optical density (A) value: 7 115.3±1 797.2 vs. 22 085.5±4 892.2, P< 0.05], and this phenomenon was more prominent in circular muscle layer. Bax and NF-κB were densely distributed, and their expressions were upgraded obviously [Bax (A value): 33 802.6±5 778.0 vs. 7 984.4±1 804.5, NF-κB (A value): 2 465.9±664.8 vs. 1 572.6±256.0, bothP< 0.05]. This phenomenon was more outstanding in circular muscle layer. Compared with that of the model group, the expression of Bcl-2 protein was stronger obviously in intestinal smooth muscle in Dachengqi decoction group (A value: 12 458.6±2 491.1 vs. 7 115.3±1 797.2,P<0.05). The expressions of Bax and NF-κB were down-regulated obviously [Bax (A value): 12 529.2±2 018.5 vs. 33 802.6±5 778.0, NF-κB (A value): 1 843.1±373.6 vs. 2 465.9±664.8, bothP< 0.05], and the change was more obvious in circular muscle layer.Conclusions Dachengqi decoction may promote recovery of gastrointestinal motility through an increase of Bcl-2 expression in nuclear membrane, thus preventing translocation of Bax to mitochondrion, thereby reduces mitochondrial damage in MODS.

The clinical effect of traditional Chinese medicine dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury/acute respiratory distress syndrome undergoing mechanical ventilation / 中国中西医结合急救杂志

Objective To explore the clinical effect of traditional Chinese medicine (TCM) dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury / acute respiratory distress syndrome(ALI/ARDS)undergoing mechanical ventilation. Methods A prospective,randomized controlled trial was conducted. Ninety-six ALI/ARDS patients admitted in intensive care unit(ICU)and treated with mechanical ventilation in Tianjin First Central Hospital were chosen and randomly divided into traditional Chinese medicine(TCM) group and conventional therapy group using a random number table,48 patients in each group. Conventional therapy alone was used in conventional therapy group,and TCM therapy of primarily using Dachengqi decoction combined with conventional therapy was applied in TCM group〔Dachengqi decoction was composed of mongolian milkvetch root 15 g, pilose asiabell toot 15 g,Chinese angelica 10 g,officinal magnolia bark 10 g,tangerine peel 10 g,immature tangerine fruit 10 g,peach seed 10 g,white peony root 12 g,red peony root 12 g,immature bitter orange 6 g,mongolian dandelion herb 30 g,radish seed(stir-fried)30 g,foxtail millet sprout 20 g,barley sprout 20 g,glauber salt 9 g (with water),rhubarb 10 g(added in water at last)〕,one dose orally taken daily for 28 days. The intra-abdominal pressure(IAP),gastrointestinal diseases in TCM symptom score and the incidence of gastrointestinal dysfunction were compared between the two groups before treatment and on the 3rd,6th and 8th day after treatment. Results There were no statistical significant differences in IAP and TCM symptom scores between the two groups before treatment (both P>0.05),but after treatment with the prolongation of therapeutic time the IAP and TCM symptom scores were decreased gradually compared with those before treatment,having reached the valley value on the 18th day and the changes in TCM group were more remarkable〔IAP(mmHg,1 mmHg=0.133 kPa):0.91±0.69 vs. 2.08±0.92, TCM symptom score:48.33±10.41 vs. 88.33±20.21,both P<0.05〕. In the TCM group,the incidences of the untoward symptoms and signs of gastrointestinal dysfunction such as bleeding of stress ulcer,toxic intestinal paralysis, abdominal distension,diarrhea and so on were lower than those in conventional therapy group〔stress ulcer bleeding:16.7%(8/48)vs. 39.6%(19/48),toxic intestinal paralysis:16.7%(8/48)vs. 43.8%(21/48),abdominal distension:10.4%(5/48)vs. 37.5%(18/48),diarrhea:6.3%(3/48)vs. 33.3%(16/48),all P<0.05〕. Conclusion Addition of TCM Dachengqi decoction on conventional treatment can effectively lower the incidence of gastrointestinal dysfunction in treatment of patients with ALI/ARDS undergoing mechanical ventilation.

Effect of Dachengqi decoction on expression of triggering receptor on myeloid cell 1 in sepsis rats / 中国中西医结合急救杂志

Objective To study the effect of Dachengqi decoction on expression of triggering receptor on myeloid cell 1(TREM-1)in septic rats in order to further provide a theoretical basis concerning the mechanism of this decoction for treatment of sepsis. Methods 100 male Sprague-Dawley(SD)rats were randomly divided into five groups:normal control,sham operation,sepsis model,low-dose and high-dose Dachengqi decoction groups (each,n=20). The sepsis models were reproduced by cecal ligated perforation(CLP). The low-dose and high-dose Dachengqi decoction groups were lavaged separately by low dose(5 mL/kg)and normal dose(10 mL/kg)Dachengqi decoction at 2 hours before CLP and after CLP twice per day(interval 8 hours),and the other three groups were lavaged with 10 mL/kg normal saline. Five rats in each group were killed randomly at the time points of 6,12,24,48 hours after CLP;the abdominal aorta blood and the liver tissue were collected. The plasma levels of TREM-1,interleukin-6 (IL-6),tumor necrosis factor-α(TNF-α)were tested by enzyme linked immunosorbent assay(ELISA). The expression level of TREM-1 mRNA in the liver was measured by reverse transcription - polymerase chain reaction (RT-PCR). Results Compared with normal control group and sham operation group, the plasma levels of TREM-1, IL-6, TNF-α and the expression of liver TREM-1 mRNA were increased significantly in model group. Compared with model group,the above indexes in low-dose and high-dose Dachengqi decoction groups were reduced obviously,the changes being more marked in the high-dose group;the levels of TREM-1,IL-6 at 6 hours after operation and the levels of TNF-αand TREM-1 mRNA at 24 hours after operation in high-dose group were lower than those of low-dose group〔6 hours TREM-1(ng/L):179.19±4.43 vs. 213.86±2.84,6 hours IL-6 (ng/L):136.80±7.70 vs. 162.90±3.87;24 hours TNF-α(ng/L):71.61±5.07 vs. 108.53±6.29,24 hours TREM-1 mRNA:24.33±3.16 vs. 27.22±3.34,all P<0.05〕. Conclusion The partial mechanism of the efficacy of Dachengqi decoction for treatment of sepsis was probably related to the inhibition of TREM-1 expression.

Compound Dachengqi Decoction and Polyethylene Glycol Electrolyte Powder in the Effect of Colonoscopic Examination / 浙江中医药大学学报

Objective The effects of compound Dachengqi Decoction and polyethylene glycol electrolyte powder in the effect of combined application of bowel preparation before colonoscopy.[Methods]From 2007 January to 2013 May, the outpatient clinic underwent endoscopy in 453 cases of patients, the patients were randomly divided into control group(192 cases) and compound Dachengqi Decoction group(261 cases). Colonoscopy bowel cleaning to control group with compound polyethylene glycol electrolyte powder; compound Dachengqi Decoction group were treated with compound Dachengqi Decoction and polyethylene glycol electrolyte powder; carry on the analysis comparison of related clinical indexes during colonoscopy in patients of 2 groups.[Results]Occurrence of Fufang Dachengqi Decoction group in the time of taking medicine and endoscopic doctor on intestinal cleaning satisfaction and the adverse reactions were superior to the control group, the difference was statistical y significant. [Conclusion]Fufang Dachengqi Decoction and polyethylene glycol electrolyte powder combined in application is effective, safe, fast, easy to be accepted by patients bowel preparation. It is conducive to the diagnosis and treatment of endoscopic, also suitable for intestinal bowel preparation before the operation, it is worthy of popularization and application.

Comparison of the rat models of liver cancer spleen deficiency established by Dachengqi and Xiaochengqi decoctions / 中国实验动物学报

Objective To explore the establishing methods and differences of rat models of spleen deficiency and spleen deficiency liver cancer using the traditional Chinese medicine Dachengqi and Xiaochengqi decoctions .Methods Spleen-deficiency rat models were developed by multifactor methods:bitter-cold purgation ( Dachengqi or Xiaochengqi de-coction), cold-wet environment, tiredness, and fasting on alternate days for 30 days.Seven days after spleen-deficiency modeled,liver cancer in the spleen-deficiency rats and normal rats was developed by subcutaneously inoculation of Walker -256 carcinoma cell line in nude mice and then transplanted into rat livers .Liver cancer models were observed for 35 days. Sixty 3-week old male Wistar rats were randomly distributed into 4 groups: normal group , liver cancer model group , and Dachengqi and Xiaochengqi decoction groups .Degree of spleen deficiency , changes of the body-weight, survival time and tumor formation were recorded .Results Spleen deficiency rat models were successfully established .The weight gain of rats in the spleen-deficiency groups was significantly inhibited (P<0.01), and during the first 20 days (but not later) the average body weight of the Dachengqi decoction group was significantly higher than that of the Xiaochengqi decoction group (P<0.05).Spleen-deficiency scores of rats in the Xiaochengqi and Dachengqi groups were higher than those in the blank tumor group, especially in the Xiaochengqi group (P<0.01).The total tumor formation rate was 91.1%and 80%in the blank tumor groups , and 93.3%in both Xiaochengqi and Dachengqi groups , respectively .The average survival time of Xi-aochengqi group was lower than that of the blank tumor and Dachengqi groups ( P<0.01 and P<0.05 ) .The cumulative survival rate of the Xiaochengqi group and rats with a higher spleen-deficiency score was lower than that of the other groups (P<0.05).Conclusions Xiaochengqi decoction may induce spleen deficiency more seriously than Dachengqi decoction , and spleen deficiency may be an important unfavorable prognostic factor for rat models of liver cancer .

Effect of Dachengqi decoction on pancreas aquaporin 1 in rats with acute necrotizing pancreatitis / 中华胰腺病杂志

Objective To detect the expression of aquaporin 1 in pancreas of rats with acute necrotizing pancreatitis (ANP) and to study the effect of Dachengqi decoction on it.MethodsOne hundred and sixty male SD rats were randomly divided into control group ( C group,n =32 ),ANP group ( n =32),Dexamethasone group (De group,n =32),Acetazolamide group (A group,n =32) and Dachengqi decoction group (DD group,n =32).ANP model was induced by retrograde injection of 5％ sodium taurocholate into the biliary and pancreatic duct.Rats in De group received dexamethasone (4 mg/kg) intravenously after ANP induction; while rats in A group received 1 ml acetazolamide via gastric lavage 2 h before ANP induction; rats in DD group received 2 ml Dachengqi decoction via gastric lavage 48,24,2h before ANP induction; rats in C group received laparotomy.Eight rats in each group were sacrificed at 3 h,6 h,12 h and 18h after induction of ANP models.Quantity of ascites and levels of serum amylases were measured.Pathological changes in pancreas tissue were detected by HE and electron microscope.Capillary permeability in pancreas tissue was detected by Evans Blue (EB) extravasations method.AQP1 expression in pancreas tissue was detected by real-time PCR and Western blotting.ResultsLevels of serum amylase in ANP group was significantly higher,and the pancreatic injuries were obvious ; the levels of serum amylase in De group and DD group was lower than that in ANP group,and the pancreatic injuries were attenuated.The levels of serum amylase in A group were higher than that in ANP group,and the pancreatic.injuries were more severe than that in ANP group.Six hours after ANP induction,the levels of EB in pancreas were (13.44 ±2.56),(126.35 ± 14.80),(86.31 ± 14.46),( 108.99 ± 15.07 ),(78.29 ± 16.85 ) mg/L In C group,ANP group,De group,A group and DD group,and the expression of AQP1 mRNA in pancreatic tissue was ( 170.07 ± 22.48 ) ％,( 83.93 ± 8.98 ) ％,( 117.09 ±10.70 ) ％,( 69.00 ± 8.98 ) ％,( 112.82 ± 11.79 ) ％ ; and the expression of AQP1 protein was 0.23 ± 0.06,0.10 ±0.02,0.32 ±0.03,0.13 ±0.02,0.45 ±0.04.The content of EB in ANP group was higher than that in C group,while the expression of AQP1 mRNA and protein in ANP group was significantly lower than that in C group (P ＜ 0.05 ).The content of EB in De group and DD group was significantly lower than that in ANP group,while the expression of AQP1 mRNA and protein was significantly higher than that in ANP group (P ＜ 0.05).ConclusionsAQP1 plays an important role in the pathogenesis of capillary endothelial barrier dysfunction in rats with ANP.Dachengqi Decoction can attenuate pancreatic injuries of rats by regulating the expression of AQP1.

Effect of Dachengqi Decoction on NF-κB p65 Expression in Lung of Rats with Partial Intestinal Obstruction and the Underlying Mechanism / 华中科技大学学报（医学）（英德文版）

To investigate the effect of Dachengqi decoction on NF-κB p65 expression in lung of rats with partial intestinal obstruction and the underlying mechanism,30 SD rats were randomly divided into three groups: sham-operation group,model group and Dachengqi decoction treatment group (Dachengqi group),with 10 animals in each group.The models were made by partially ligating their large intestines outside the body.The pathological changes were analyzed by HE staining.The expression of NF-κB p65 in rats lung were measured by using real-time polymerase chain reaction and immunohistochemistry respectively.Moreover,the expression of caveolin-I in rats lung was also measured to.Increased edema,interstitial thickening,hemorrhage,and infiltration of inflammatory cells were found in the model group.In contrast,this change was significantly reduced in Dachengqi group as compared with model group.In addition,the up-regulated caveolin-1 and NF-κB p65 were also suppressed by Dachengqi decoction in lung of rats with partial intestinal obstruction.We are led to concluded that the caveolin-1-NF-κB pathway plays an important role in the development of lung injury of rats with partial intestinal obstruction and Dachengqi decoction could down-regulate the expression of caveolin-1 and NF-κB p65 in lung of rats with partial intestinal obstruction.

The effects of Rheu compositus on alveolar macrophages NF-κB activity and inflammatory cytokine expres-sion in rats with ARDS / 中华急诊医学杂志

Objective Tostudy the effects ofRheu compositus (Dachengqi Decoction, DD) on the NF-κBactivity of alveolar macrophages in ARDS rats and its inflammatory cytokine expression, and hence to explore the molecular mechanism of the anti-inflammatory effects of DD. Method The 65 male Wistar rats were randomly di-vided into the control group (n = 12), the ARDS model group (n = 21), the DD treatment group (n = 16) and the dexamethasone treatment group (n = 16). The rots of model group received 1 mg/(kg·0.5 mL) LPS injected intra-poritoneally and LPS in dose of 5 mg/(kg·0. 5 mL) was administrated by slow dropping endotracbeally 16 hours later. Modeling was successfully established 6 hours later evidenced by arterial gas analysis. The rats of con-trol group received 0.5 mL normal saline injected intravenously through tail vein instead of LPS. Three days after establishment of modeling, DD was given to rats of DD treatment group by intragastric instillation for 3 days in dose of 2.31 g/(kg·d),in which the weight of drug was calculated on the basis of dried herbal medicine. In dexam-ethasone treatment group, rats had intra-peritoneal injection of 2 mg/kg dexamethasone for 3 days after modeling was established. Seventy-two hours later, the arterial blood gas analysis and pathological study were carried out, in rats of all groups, and the findings were graded. The levels of TNF-α, IL-1 and IL-10 both in the plasma and in the brenchoalveolar lavage fluid were determined by using the enzyme linked immunosorbent assay (ELISA). Besides the nucleopretein concentration of pulmonary alveolar macrophage (PAM) was maeasuredwith the BAC method, and the NF-κB activity was determined with the Western Blotting, and with the evaluation of the DD' s effect on the transcription activity of PAM inflammatory cytokines. All the experimental data were processed by the SPSS 13.0 for statistical analysis. The analysis of variance was used for the comparison between groups, and P < 0. 05 showed the statistical significance of the difference. Results DD didn' t significantly reduce the TNF-α level [(510.97±76.20) pg/mL,(476.16±98.03) pg/mL, P >0.05], but significantly deceased the plasma IL-1 level [(381.99±34.30) pg/mL, (300.69 ± 50.99) pg/mL, P <0.05]. At the same time, there was no signif-icant changes in the plasma IL-10 level [(345.96 ± 67.72) pg/mL, (345.30 ± 78.52) pg/mL, P > 0.05]. Whereas TNF-α level in BALF was significantly decreased [(130.94 ± 33.51) pg/mL, (106.59 ± 26.64) pg/ mL, P < 0. 05, so was the IL-1 level in BALF (82.5 ± 25.36) pg/mL, (63.89 ± 22.96) pg/mL, P < 0. 05], but IL-10 level in the BALF was significantly increased[(77.09 ± 26.05) pg/mL, (148.05 ± 53.50) pg/mL, P <0.01]. DD significantly reduced the nueleoprotein level of PAM[(5.35 ± 2.44) μg/μL, (3.54 ± 2.01) μg/ μL, P < 0.05]and significantly inhibited the NF-κB activity [electrophoretic band optical density × area/consult mtio:(1.45±0.71),(1.11±0.28), P <0.05]aswell. Conclusions DD regulated systemic pro-inflammato-ry media/anti-inflammatory media balance in rats with ARDS by mainly reducing the level of IL-1. The regulatory effects of DD on the local lung injury not only inhibit the producing of TNF-α and IL-1 level,but also increase the IL-10 level to reestablish the local pro-inflammatory factors/anti-inflammatory factors balance so as to inhibit the lo-cal excessive irranune response. DD inhibits the NF-κB activity in the PAM of ARDS rats so as to restrain the pro-duction of pro-inflammatory cytokines (TNF-α and IL-1). This kind of multi-target bidirectional regulation plays an active role in regulating the immune balance and protecting the target organ from the excessive injury.

Three Chengqi decoctions in clinical application of mental disease / 中华中医药杂志

Three Chengqi decoctions originated from Treatise on Cold Pathogenic Diseases refers to Tiaoweichengqi decoction,Xiaochengqi decoction and Dachengqi decoction.This article introduced clinical application of the three Chengqi decoctions for mental disease.This paper pointed out that treating for psychiatric patients with YangmingFushi syndrome with the corresponding decoction according to the degree of interior heat and excess can achieve satisfactory curative effects.Meanwhile,the author also put forward his own views on some problems that should be pay attention to in clinical application of the three Chengqi decoctions such as the dose of agents in decoction and the decocting methods.

Immunoregulatory effect of Dachengqi decoction on endotoxic ARDS in rats / 中国病理生理杂志

AIM:To investigate the effect of Dachengqi decoction(DD)on the acute respiratory distress syndrome(ARDS)in rat model induced by endotoxin "two-hit".METHODS:48 healthy male Wistar rats were randomly divided into 4 groups:control group,ARDS model group,ARDS+DD treatment group and ARDS+dexamethasone treatment group(12 in each group).E.coli lipopolysaccharide(LPS)"two-hit" induced ARDS model in rats was established.The arterial blood gas analysis,lung wet/dry weight(W/D)ratio and lung tissue pathology observation and scoring were measured to evaluate the pharmacological effects of DD on ARDS.The levels of TNF-?,IL-1 and IL-10 were determined by ELISA to explore the immune regulatory mechanism of DD.RESULTS:(1)Treatment with DD significantly improved blood pressure in rats,increased oxygen saturation,decreased lung wet/dry weight ratio and lung injury score,relieved pulmonary edema and the inflammatory responses.(2)DD suppressed the productions of systemic and pulmonary pro-inflammatory mediators and promoted the release of anti-inflammatory mediators in lung.CONCLUSION:The inhibitory effects of DD treatment on pulmonary inflammatory response are not only related to reducing the extent of systemic inflammatory response,but also promote pulmonary anti-inflammatory production and regulate the balance of pulmonary pro-inflammatory mediators and anti-inflammatory cytokines.This specific regulatory effect protects the target organ from excessive inflammatory organ injury,discloses that DD has advantages in the treatment of endotoxic ARDS.