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ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg-1） and positive drug （celecoxib， 0.03 g·kg-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E2 （PGE2）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE2 in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.
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OBJECTIVE@#To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.@*METHODS@#Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).@*RESULTS@#Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.@*CONCLUSION@#LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
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Animals , Mice , Acetylation , Inflammation Mediators , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
It has become a consensus that there is a correlation between psoriasis and obesity, but the exact mechanism is not yet clear. Studies demonstrate that common inflammatory pathways and insulin resistance may contribute to the association between psoriasis and obesity. Understanding the impact of obesity on the occurrence and treatment of psoriasis will be beneficial to the treatment of psoriasis.
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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.
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@#AIM:To explore the effects of recombinant human growth hormone(rHGH)on early rehabilitation in rabbit corneal epithelial wound. <p>METHODS:Thirty-two New Zealand rabbits were selected to establish the corneal epithelial defects models. One eye was treated with normal saline(NC group)and the other eye was treated with 20nmol/L rHGH(rHGH group)in a randomized double-blinded way. The corneal healing process was monitored by the corneal fluorescein staining scores at 0h, 24h, 48h, and 72h after the surgery. The central corneal sensitivity was detected by Cochet-Bonnet corneal esthesiometer and the concentrations of inflammatory mediators interlecukin-1α(IL-1α), interlecukin-17(IL-17), interlecukin-21(IL-21), Leptin, matrix metalloproteinase-9(MMP-9)and tumor necrosis factor-α(TNF-α)in collected tears were measured by multiplex antibody microarray. <p>RESULTS: The corneal epithelial healing rates of the NC group and rHGH group were(62.52±6.73)% and(79.62±10.62)%(<i>P</i><0.05),(90.56±9.57)% and(98.43±3.65)%(<i>P</i><0.05)at 48h and 72h postoperatively. The central corneal sensitivity of rHGH group(4.22±0.26)cm was better than that in NC group(3.22±0.42)cm at 48h after surgery(<i>P</i><0.05). The expressions of TNF-α and IL-1α increased in both groups at each time point after operation, and the expressions in NC group were higher than those in the rHGH group. Both groups had higher MMP-9 concentrations in the tear fluid at 24 and 48h postoperation in comparison with the point before the operation. The MMP-9 expression in NC group was higher than that in the rHGH group at 48h postoperatively. The expressions of IL-21 in NC group were higher than those in the rHGH group at 24 and 48h postoperation in comparison with the point before the operation(<i>P</i><0.05). No significant differences in tearIL-17 and Leptin were observed between groups before and after surgery(<i>P</i>>0.05).<p>CONCLUSION: Topical application of rHGH can accelerate the early stage of rabbit corneal epithelial wound healing <i>in vivo</i>.
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Objective@#To analyze the impact of Pringle’s maneuver on postoperative serum inflammatory mediator levels and prognosis in hepatitis B virus-related hepatocellular carcinoma (HBV related HCC) patients.@*Methods@#A retrospective study was conducted on 157 HBV related HCC patients who underwent treatment at the Chinese PLA General Hospital from January 2016 to December 2017. There were 128 males and 29 females. The mean age was (54.5±12.1) years. These patients were divided into 106 patients who underwent Pringle’s maneuver (the Pringle’s maneuver group). The remaining patients were in the Occlusion-free group. All patients were detected inflammatory mediator levels including the various interleukins (IL) and were regularly followed up. The recurrence-free survival was evaluated by the Kaplan-Meier method, and compared with the log-rank test. The relationship between the Pringle’s maneuver and risks of postoperative tumor recurrence of these patient were estimated by the univariate and multivariate Cox regression models.@*Results@#On postoperation day 1 and day 3, the serum IL-1 and IL-6 levels of the Pringle’s maneuver group were significantly higher than the Occlusion-free group [5.0(5.0, 12.0)ng/L vs. 5.0(5.0, 5.0)ng/L], [122.0(74.5, 173.8)ng/L vs. 80.0(40.0, 120.0)ng/L]; [5.0(5.0, 10.0)ng/L vs. 5.0(5.0, 5.0)ng/L], [78.3(42.8, 138.5)ng/L vs. 48.1(30.1, 75.0)ng/L]. On day 5, the serum IL-1 and IL-8 levels were also significantly higher than the Occlusion-free group [5.0(5.0, 5.3)ng/L vs. 5.0(5.0, 5.0)ng/L], [100.6 (44.2, 186.5)g/L vs. 68.0(36.3, 112.0)ng/L] (all P<0.05). There were 42 and 27 patients who did not develop recurrence in the Pringle’s Maneuver group and the Occlusion-free group, respectively. The recurrence-free survival rates of the Pringle maneuver group and the Occlusion-free group were 40.0% and 52.9%, respectively. There were no significant differences between the two groups (P>0.05). The multivariate Cox regression model suggested that there was no significant correlation between Pringle’s maneuver and recurrence free survival of these patients with HBV related HCC.@*Conclusions@#Pringle’s maneuver could significantly elevate the postoperative serum IL-1, IL-6, IL-8 levels, but it was not related with an increased risk of postoperative tumor recurrence.
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Objective To systematically review the effect of Qingre Jiedu and Liangxue Sanyu method in patients with sepsis,and to discuss its effect in the treatment of sepsis.Methods The randomized controlled trials (RCTs) on the treatment of Qingre Jiedu and Liangxue Sanyu method for sepsis published on PubMed,Embase,Web of Science,CNKI and Wanfang database from the construction to December 31st,2017 were searched by electronical way.Conventional treatment measures for sepsis,such as fluid resuscitation,maintenance of hemodynamic stability,anti-infection,improvement of tissue perfusion,maintenance of organ function and nutritional support were used in the control group.While traditional Chinese medicine treatment based on Qingre Jiedu and Liangxue Sanyu method were applied in the experimental group besides the conventional treatment,including Chinese patent medicine or Chinese herbal medicine.The main outcome was 28-day mortality,and the second outcome was acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ),coagulation function,inflammatory mediators,procalcitonin (PCT),lactic acid (Lac),and the length of intensive care unit (ICU) stay.Two researchers independently searched literatures,collected data and evaluated risk bias.The statistical analysis was completed by RevMan 5.3 and STATA 13.0 software.The funnel plot and Egger test were used to evaluate the potential publication bias of the main outcomes.Results A total of 20 RCTs were enrolled in this Meta-analysis,including 1 347 patients,with 667 patients in the control group and 680 patients in the experimental group.Comprehensive risk bias assessment showed that the risk bias of 11 RCT items was unknown,and the risk bias of 9 RCT items was high.Meta-analysis results showed that compared with the control group,the 28-day mortality of the experimental group was significantly lowered [relative risk (RR) =0.54,95％ confidence interval (95％CI) =0.45-0.65,P ＜ 0.00001],the 7-day APACHE Ⅱ score was significantly lowered [mean difference (MD) =-3.86,95％CI =-4.82 to-2.90,P ＜ 0.00001],the 7-day prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly shortened (PT:MD =-1.72,95％CI =-2.29 to-1.14,P ＜ 0.00001;APTT:MD =-4.36,95％CI =-5.81 to-2.91,P ＜ 0.000 01),the 7-day D-dimer was slightly improved (MD =-0.13,95％CI =-0.37-0.11,P =0.29),the 10-day interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly decreased (IL-6:MD =-40.33,95％CI =-59.55 to-21.11,P ＜ 0.000 1;TNF-α:MD =-7.26,95％CI =-11.31 to-3.21,P =0.000 4),the 7-day Lac was significantly declined (MD =-1.30,95％CI =-1.91 to-0.68,P ＜ 0.000 1),but no significance in PCT (MD =-1.57,95％CI =-3.25-0.11,P =0.07) or the length of ICU stay (MD =-4.02,95％CI =-8.60-0.56,P =0.09)was found.The results of publication bias assessment showed that 19 studies reported 28-day mortality were basically "funnel-shaped" distribution without potential publication bias (P =0.336).Conclusion The Meta-analysis showed that Qingre Jiedu and Liangxue Sanyu method may reduce the release of inflammatory mediators,improve the coagulation function,and reduce the 28-day mortality in patients with sepsis.
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Objective To explore the protective mechanism of glycogen synthase kinase-3β(GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. Methods SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-κB p65 (NF-κB p65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor -α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Results Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-κB p65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L):195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-κB p65 in the nucleus was significantly decreased; the expression of p-GSK-3β(Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Conclusions Blockade of GSK-3βactivity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-κB and its related inflammatory mediators.
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OBJECTIVE@#Based on the establishment of a rat model of trigger point, this study was to intervene with warm acupuncture, and to evaluate the effect on pathological morphology and pain-induced inflammation of the rat model by microscopic pathology and microdialysis.@*METHODS@#Sixty-four SD rats were randomly divided into group A (blank control), group B (model control) and group C (model and intervention control). Groups A and B were divided into 3 groups (A0, A1, A2 and B0, B1, B2), the group C was divided into 2 groups (C1 and C2). The MTrPs model was established in both groups B and C, warm acupuncture intervention were given to the C1 group for 7 days and the C2 group for 15 days. Rats were sacrificed in batches. MTrPs were locally sampled and stained with hematoxylin-eosin after the preparation. The pathological changes were observed under light microscopy. The iocal interleukin-1β and prostaglandin E2 were detected by microdialysis technique.@*RESULTS@#Microscopically, the muscle fibers of the model were arranged disorderly, broken, twisted, local fibrosis, contracture thickening and so on; macrophage and other inflammatory cell invasion in local area and a large area of adhesion occurred on the contracture nodule, the pathological state of local muscle fibers was significantly improved after warm needle intervention, local microvascular formation and maturation, local muscle fiber repair. After successful modeling, the amount of interleukin-1β and prostaglandin E2 in group B0 was significantly higher than that in group A0 before warm needle intervention (0.05). Group C1 and B1 were significantly higher than group A1 (<0.01); warm needle intervention for 15 days, the amount of interleukin-1β and prostaglandin E2 in group C2 were lower than those in group B2 (<0.05), but those in group C2 and B2 were significantly higher than group A2 (<0.01), and the amount of interleukin-1β and prostaglandin E2 in group C2 was lower than group C1 (<0.05).@*CONCLUSIONS@#The modeling method of exercise combined hitting used in this study was proved to be effective by histopathology; warm acupuncture can improve the pathological and inflammatory state of local muscle fiber in myofascial pain trigger of rat, promote local microvascular formation and maturation, and help the trigger point local muscle fiber repair.
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Animals , Rats , Acupuncture Therapy , Inflammation Mediators , Myofascial Pain Syndromes , Rats, Sprague-Dawley , Trigger PointsABSTRACT
Objective: To investigate the effects of procyanidin B2 on the expression of inflammatory mediators in human periodontal ligament cells (hPDLCs) induced by Porphyromonas gingivalis lipopolysaccharide (LPS). Methods: hPDLCs were cultured using tissue explant method in vitro. The effect of procyanidin B2 on the cell viability of hPDLCs was detected by MTT assay. hPDLCs were stimulated by P. gingivalis LPS after treatment with procyanidin B2 for 1 h. The expressions of IL-1β, IL-6, and IL-8 mRNA and proteins were detected by real-time PCR and ELISA assay. Reactive oxygen species (ROS) in the cytoplasm was observed under fluorescence microscope. Nitric oxide (NO) in the supernatant was detected by Griess assay. Results: 100.00 µg/mL procyanidin B2 could enhance the cell viability of hPDLCs. Procyanidin B2 could inhibit the expressions of IL-1β, IL-6, and IL-8 mRNA and proteins in hPDLCs. It could also downregulate ROS and NO in hPDLCs induced by P. gingivalis LPS. Conclusion: Procyanidin B2 can play an anti-inflammatory role by inhibiting inflammatory mediators in hPDLCs induced by P. gingivalis LPS.
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Aim To study the intervention effect of tet- ramethylpyrazine(TMP) on human microvascular endothelial cells (HMECs) inflammatory response induced by activated complement alternative pathway and the possible molecular mechanisms. Methods HMECs were pretreated with different concentrations of TMP, and then exposed to the activated products of the complement alternative pathway which was prepared by cobra venom factor( CVF). The supernatant was removed and assayed for expression of the adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and the inflammatory mediator(IL-6 and TNF-ot) by using ELISA reagent kits. The nucleus transcriptional activity of NF- kB was measured by the dual luciferase reporter assay ? system. Results The adhesion molecules, inflammato ry mediator and nucleus transcriptional activity of NF- kB increased after HMECs were exposed to the products of the activated complement alternative pathway. The up-regulation of ICAM-1, VCAM-1, E-selectin, IL-6, TNF-a and the nucleus transcriptional activity of NF-kB were inhibited by various concentrations of TMP in a dose-dependent manner. Conclusions TMP can effectively reduce inflammatory response of HMECs in-duced by the activated complement alternative pathway , and the mechanism may be highly related to inhibition of nucleus transcriptional activity of NF-kB.
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Objective To investigate the effect of ulinastatin on myocardial injury in rats with sepsis.Methods Thirty male SD rats were randomly (random number) divided into 3 groups:sham operation group (Sham group,n=10),sepsis group (sepsis group,n=10) and ulinastatin group (UTI group,n=10).The sepsis model of the rats was subjected to cecal ligation and puncture (CLP).Rats of UTI group were given 200 000 U/kg ulinastatin at 6 hour after modeling,and dosing was repeated every 12 h.Blood samples were collected from inferior vena cava at 6,12,24,36 h after modeling for determination of cardiac troponin-Ⅰ (cTnI) and the inflammatory factor by ELISA,then the rats were sacrificed and hearts were removed for myocardial tissue stained with hematoxylin eosin (HE) staining,the expression of Bax/Bcl-2 protein level and myocardial cell apoptosis were detected by TUNEL.The level of caspase-3 protein in myocardial tissue was detected by Western-blot.Results The level of cTnI (ng/mL) in serum in UTI group at 6,12,24 and 36 h after modeling were significantly lower compared with sepsis group(P＜0.05).The protein expression levels of TNF-α and IL-6 (ng/mL) in group UTI were higher than those in Sham group,but was significantly lower than those in Sepsis group (P＜0.05).HE staining showed that inflammatory cell infiltration present in myocardial cells,edema and vacuole formation were observed in sepsis group,while those were significantly attenuated in UTI group compared with sepsis group.UTI increased the level of myocardial Bcl-2 protein in the rats (P＜0.05),and reduced the level of myocardial Bax protein (P＜0.05).TUNEL and HE staining showed apoptosis cells in UTI group was significantly reduced compared with sepsis group [(32.2±4.8)％ vs.(58.4±5.6)％,P＜0.05];Western-blot method showed the level of Caspase-3 protein in UTI group was higher than that in group sham (0.32±0.048) vs.(0.12±0.03),P＜0.05],but significantly lower than that of Sepsis group [(0.32±0.048) vs.(0.55±0.052),P＜0.05].Conclusions Ulinastatin can reduce proinflammatory mediators release in the blood of sepsis rats,and inhibit the apoptosis of myocardial cells protecting myocardial cells through the regulation of the Caspase-3 pathway during sepsis.
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Objective To investigate the effect of aspirin and ticagrelor or clopidogrel anticoagulant therapy on platelet aggregation,endothelial function and levels of inflammatory mediators in patients with acute coro-nary syndrome(ACS)after coronary stent implantation(PCI).Methods 100 cases of patients with ACS who underwent coronary stent implantation in our hospital from April 2014 to May 2016 were enrolled in the stud-y.The patients were randomly divided into the observation group and the control group by random number ta-ble method,50 cases in each group.The observation group were treated with aspirin and ticagrelor anticoagu-lant therapy after operation,while the control group were treated with aspirin and clopidogrel anticoagulant therapy.All patients were followed up for 1 year.The platelet aggregation rate within 1 year of medication, levels of serum endothelin-1(ET-1),nitric oxide(NO),plasminogen activator inhibitor-1(PAI-1),high-sen-sitivity C reactive protein(hs-CRP),interleukin-6(IL-6)and soluble CD40 ligand(sCD40L)were compared between the two groups.The outcome events and adverse reactions were recorded.Results 1 month,6 months and 1 year after treatment,the platelet aggregation rates in the observation group were lower than those in the control group(P<0.05).After treatment,levels of serum ET-1,PAI-1,hs-CRP,IL-6 and sCD40L were sig-nificantly lower in the observation group than the control group(P<0.05),while NO level was higher than the control group(P<0.05).The incidence rates of outcome events and adverse reactions in the observation group were slightly lower than those in the control group(6.00% and 8.00% vs.10.00% and 10.00%,P>0.05).Conclusion The effect of aspirin combined with ticagrelor anticoagulant therapy is better than that of aspirin combined with clopidogrel anticoagulant therapy in patients with ACS after PCI.The former can signif-icantly improve platelet aggregation,endothelial function and levels of inflammatory mediators,and it is safe and reliable.
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Objective:To investigate the effects of n-3 fish oil fatty emulsion on fatty acid profile and lipid mediator,immune regulation mechanism and anti-inflammatory effect of inpatients underwent total gastrectomy.Methods:In a prospective,double-blind,and randomized controlled trial,60 patients underwent total gastrectomy were divided into two groups,therapy group and control group.The control group was given routine therapy while the therapy group was given routine therapy and fish oil.The day before the operation,1,4 and 8 days after the operation,The lipid metabolic Indices,including free fatty acids spectrum were detected;The inflammation indicator,including c-reactive protein(CRP) and interleukin(IL-1,lL-6),tumor necrosis factor alpha(TNF-α) were tested;The cellular immune function,including HLA-DR expression rate,the level of T cell subgroup were detected with flow cytometry.The clinical outcome indicators including APACHE Ⅱ score,postoperative infection and MODS incidence,postoperative hospitalization days,hospitalization mortality were observed.Results:There was no significant difference between Fish oil group and control group in age,sex and BMI,the serum levels of inflammatory cytokines,the HLA-DR expression rate,level of T cell subgroup,APACHE Ⅱ score,etc.(P＞0.05),so the two groups are comparable.Compared with control group,the n-6/n-3 PUFAs ratio drops,AA content decreased,but the content of EPA and DHA is increased,in fish oil group,decreased in fish oil group (P＜0.05);Compared with control group,serum concentration of CRP,IL-6 and TNF-α in patients of therapy group were significantly reduced,and clinical outcome improved.There was no difference in the expression of T cell subgroup between two groups.Conclusion:Application of n-3 fish oil fat emulsion,can lower the n-6/n-3 PUFAs ratio,reduce the AA content in serum,but the content of EPA and DHA is increased;N-3 fish oil fat emulsion can reduce serum after total gastrectomy,IL-1,IL-6,TNF-α inflammatory factor and the concentration of CRP,effectively reduce the inflammatory response in patients with;N-3 fish oil fat emulsion can improve the HLA-DR expression rate,reduce the immunosuppression,but had no significant effect on T cell subgroup level;N-3 fish oil fat emulsion to reduce the incidence of postoperative infection and MODS,improve patients with acute physiology,but had no significant effect on total days in hospital,mortality.
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Systemic lupus erythematosus (SLE)is an autoimmune disease,involving multiple organs and systems,and it is defined as neuropsychiatric systemic lupus erythematosus (NPSLE) when neuropsychiatric symptoms appear.The N-methyl-D-aspartate (NMDA) receptor is a kind of membrane-spanning ion channels' glutamate receptors,which mainly contains NR1 subunit and NR2 subunit.In recent years,the role of anti-NMDA-receptor antibodies in the pathogenesis of NPSLE has become a research hotspot,especially for anti-NR2 antibody.Therefore we review the research progress of the mechanism of the anti-NMDA-receptor antibodies in NPSLE in this paper.
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Objective To investigate the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on immune cells and inflammatory factors in septic rats.Methods 184 male Sprague-Dawley (SD) rats were divided into normal control group (n = 8), sham operation group (n = 48), sepsis model group (n = 64), and UC-MSCs treatment group (n = 64). An animal model of sepsis was produced by cecal ligation and puncture (CLP). In the UC-MSCs treatment group 1 mL UC-MSCs (2×106/mL) were injected intraperitoneally at 1 hour after the model establishment;the sham operation group and the sepsis model group were given the same amount of saline. Sixteen animals in each group of the sham operation group, sepsis model group, and UC-MSCs treatment group were observed for 72-hour survival rate. The percentages of CD4+ T cells and the ratio of helper T cells 1/2 (Th1/Th2) in whole blood cells were measured by flow cytometry at 12, 24, 48 and 72 hours after operation. The levels of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1), interleukin-10 (IL-10) were measured by enzyme linked immunoabsorbent assay (ELISA).Results The 72-hour survival rate of the UC-MSCs treatment group was slightly higher than that of the sepsis model group [62.5% (10/16) vs. 50.0% (8/16),χ2 = 0.509,P > 0.05]. The percentage of CD4+ T cells and Th1/Th2 ratio in the sepsis model group were significantly higher than those in the sham operation group at 12 hours after operation, and decreased as the time prolonged to 48 hours. The levels of plasma inflammatory factors were significantly higher than those of sham operation group at 12 hours after operation, TNF-α and IL-10 were decreased at 48 hours after operation, while HMGB1 continued to increase until 72 hours after operation. Compared with those in the sepsis model group, the percentages of CD4+ T cells at 12 hours and 24 hours after operation [(49.66±0.91)% vs. (59.11±1.17)%, (41.80±0.89)% vs. (49.84±0.99)%], the levels of Th1/Th2 ratio at 12, 24, 48 hours after operation (0.745±0.065 vs. 1.254±0.115, 0.407±0.077 vs. 0.806±0.061, 0.280±0.057 vs. 0.454±0.049), and the levels of TNF-α and HMGB1 were significantly reduced at 12, 24, 48 and 72 hours after operation in the UC-MSCs treatment group [TNF-α(ng/L):52.60±6.60 vs. 58.03±6.53, 71.77±8.48 vs. 147.39±11.37, 111.83±10.76 vs. 271.36±19.04, 83.09±7.43 vs. 171.04±14.06; HMGB1 (ng/L): 149.12±9.89 vs. 187.33±12.79, 192.94±14.92 vs. 442.35±52.72, 1393.67±88.86 vs. 1950.90±126.66, 1875.84±111.67 vs. 2557.12±186.01], all with statistically significant differences (allP <0.05). The level of IL-10 was significantly higher at 12, 24, 48 and 72 hours after operation (ng/L: 65.46±5.51 vs. 33.32±4.17, 86.49±5.78 vs. 63.11±5.53, 142.73±9.94 vs. 106.81±6.36, 123.74±10.90 vs. 89.90±7.71, allP <0.01).Conclusion UC-MSCs can make CD4+ T cells in early sepsis, and Th1/Th2 ratio to normal, by reducing the levels of proinflammatory factors, and increasing the level of anti-inflammatory factor, and improve sepsis immune function status, but cannot improve the survival rate of animals.
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The present study aims to investigate the effects of Xuesaitong (XST)injection on inflammation induced by OGD/reoxygenation in BV2 microglia cell and explore the underlying mechanisms.The effects of XST injection were evaluated in terms of cell viability, secretion of TNF-α, IL-1β, IL-6 and IL-10 into culture media, protein expression of p-ERK1/2, p-JNK and p-p38, and nuclear translocation of NF-κB p65. The results showed that XST injection significantly increased cell viability, suppressed release of TNF-α, IL-1β, IL-6 and IL-10 and down-regulated p-JNK1/2 and p-p38 MAPK expression in BV2 microglia cells induced by OGD/R injury, whereas it had no effect on p-ERK1/2 expression. Furthermore, XST injection suppressed nuclear translocation of NF-κB p65 in BV2 microglia after OGD/R injury. These data indicate that the neuroprotective effects of XST injection on OGD/R injury are associated with its inhibition of pro-inflammatory mediator production, down-regulation of JNK1/2 and p38 MAPK activation, and suppression of NF-κB p65 nuclear translocation in BV2 microglia cells.
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Objective@#To investigate the effect of Liangge powder on the expression of inflammatory mediators and hepatic and renal function in rats with sepsis via a preliminary analysis.@*Methods@#A total of 195 Wistar rats were randomly divided into sham-operation group (15 rats) , model group (90 rats) , and treatment group (90 rats) using a random number table, and according to the time point after modeling, the model group and the treatment group were further divided into 24, 48, and 72 hour subgroups, with 30 rats in each subgroup. Cecal ligation and puncture (CLP) was performed to establish a rat model of sepsis, and solid-phase sandwich enzyme-linked immunosorbent assay was used to measure the expression of interleukin-10 (IL-10) , interleukin-1 (IL-1) , interleukin-4 (IL-4) , and lipopolysaccharide (LPS) at 24, 48, and 72 hours after CLP. An automatic biochemical analyzer was used to measure the levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , blood urea nitrogen (BUN) , and creatinine (Cr) .@*Results@#Compared with the sham-operation group, the model group had significant increases in the serum levels of IL-1, IL-4, IL-10, LPS, BUN, Cr, AST, and ALT at 24, 48, and 72 hours after CLP (P<0.05) . Compared with the model group, the treatment group had a significant reduction in the serum level of IL-1 at 24, 48, and 72 hours after CLP, a significant increase in the serum level of IL-4 at 24 and 48 hours after CLP, and a significant increase in the serum level of IL-10 and a significant reduction in the serum level of LPS at 24 and 72 hours after CLP (P<0.05) . Compared with the model group, the treatment group had a significant reduction in ALT at 24 hours after CLP, significant reductions in BUN and Cr at 48 hours after CLP, and a significant reduction in AST at 72 hours after CLP (P<0.05) .@*Conclusion@#In the early stage of sepsis, imbalance between pro-inflammation and anti-inflammation and immunosuppression may cause hepatic and renal impairment in rats with sepsis. The traditional Chinese medicine Liangge powder can regulate inflammatory response, restore the balance between pro-inflammation and anti-inflammation, and improve hepatic and renal function in rats with sepsis.
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Objective To discuss the correlation between levels of hs-CRP,IL-6 and MMP-9 with cerebral microbleeding (CMB).Methods A total of 201 of non-acute ischemic cerebrovascular were collected and performed heal MRI+ susceptibility-weighted imaging(SWI).The patients were divided into the CMB group(49 cases) and non-CMB group(152 cases) according to the SWI examination results.The clinical data were recorded in the two groups.The levels of inflammatory mediators high-sensitivity C-reactive protein (hs-CRP),interleukin-6 (IL-6) and matrix metalloproteinase-9(MMP-9) were tested.The Logistic regression analysis was used to analyze the relation between the levels of hs-CRP,IL-6 and MMP-9 with cerebral microbleeding.Results The levels of inflammatory mediators hs-CRP,IL-6 and MMP-9 in the CMB group were significantly higher than those in the non-CMB group (P＜0.05).The logisticMultivariate logistic regression analysis showed that the levels of hs-CRP,IL-6 and MMP-9[OR value(95％CI):1.745(1.342-2.270),1.223(1.018-1.533),1.284(1.082-1.423),P＜0.05)] were the risk factors of CMB after adjusting the influence of age,sex and traditional risk factors.Conclusion The levels of inflammatory mediators hs-CRP,IL-6 and MMP-9 are closely associated with CMB,which participate in CMB occurrence.
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Objective To discuss the correlation between levels of hs-CRP,IL-6 and MMP-9 with cerebral microbleeding (CMB).Methods A total of 201 of non-acute ischemic cerebrovascular were collected and performed heal MRI+ susceptibility-weighted imaging(SWI).The patients were divided into the CMB group(49 cases) and non-CMB group(152 cases) according to the SWI examination results.The clinical data were recorded in the two groups.The levels of inflammatory mediators high-sensitivity C-reactive protein (hs-CRP),interleukin-6 (IL-6) and matrix metalloproteinase-9(MMP-9) were tested.The Logistic regression analysis was used to analyze the relation between the levels of hs-CRP,IL-6 and MMP-9 with cerebral microbleeding.Results The levels of inflammatory mediators hs-CRP,IL-6 and MMP-9 in the CMB group were significantly higher than those in the non-CMB group (P＜0.05).The logisticMultivariate logistic regression analysis showed that the levels of hs-CRP,IL-6 and MMP-9[OR value(95％CI):1.745(1.342-2.270),1.223(1.018-1.533),1.284(1.082-1.423),P＜0.05)] were the risk factors of CMB after adjusting the influence of age,sex and traditional risk factors.Conclusion The levels of inflammatory mediators hs-CRP,IL-6 and MMP-9 are closely associated with CMB,which participate in CMB occurrence.