Effect and Mechanism of Fuzheng Touxie Prescription on Immune Homeostasis of Drug-resistant Pseudomonas aeruginosa Lung Infection Rats / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Fuzheng Touxie prescription （FZTX） on the immune homeostasis of drug-resistant <italic>Pseudomonas aeruginosa</italic> lung infection in rats at different time points. Method:A total of 168 rats were divided into a blank group （<italic>n</italic>=8），a model group （<italic>n</italic>=40），a Touxie （TX） group （<italic>n</italic>=40），an early Fuzheng （FZ） group （<italic>n</italic>=40）， and a delayed FZ group （<italic>n</italic>=40）. The blank group was given distilled water by gavage， the model group was given distilled water by gavage after infection，the TX group was given clear heat and penetrate evil drug free decoction granules（3.5 g·kg^-1） by gavage after infection， the early FZ group was given Fuzheng Touxie whole formula free decoction granules（10.75 g·kg^-1） by gavage after infection， the delayed FZ group was given clear heat and penetrate evil drug free decoction granules by gavage after infection， on the third day plus Fuzheng drug free decoction granules［（3.5+10.75） g·kg^-1］ by gavage， the three treatment groups were gavaged twice a day， 2 mL each time .Each drug treatment group was divided into five groups according to five time points （3 h，1 d，3 d，5 d， and 7 d）， with eight rats in each group. The levels of tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>），high mobility group protein 1（HMGB1），interleukin-10（IL-10）， and tumor necrosis factor -<italic>α</italic>-induced protein-8-like2 （TIPE2） were measured by enzyme-linked immunosorbent assay （ELISA）， and HMGB1 protein expression level by Western blot. Result:At 3 h，the TNF-<italic>α</italic> content in the drug treatment groups was higher than that in the blank group and the model group （<italic>P</italic><0.05）. At 3 d，the TNF-<italic>α</italic> content in the early FZ group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05） and the TX group （<italic>P</italic><0.05）. At 1 d，the HMGB1 content in the TX group and the delayed FZ group was higher than that in the model group （<italic>P</italic><0.05）. At 5 d，the HMGB1 content was lower in the delayed FZ group than in the model group （<italic>P</italic><0.05）. At 7 d，HMGB1 protein expression in the model group was higher than that in the blank group （<italic>P</italic><0.05） and the early FZ group （<italic>P</italic><0.05）. At 3 d，the IL-10 content was significantly higher in both the early FZ group and the delayed FZ group than that in the model group （<italic>P</italic><0.05）. At 5 d，the IL-10 content was higher in the early FZ group than that in the TX group （<italic>P</italic><0.05）. At 7 d，the IL-10 content in the early FZ group and the delayed FZ group was lower than that in the TX group （<italic>P</italic><0.05）. At 5 d，the TIPE2 content in the early FZ group was lower than that in the model group （<italic>P</italic><0.05）. At 7 d，the TIPE2 content in the TX group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05）. Conclusion:FZTX or modified prescription can promote the inflammatory response to eliminate pathogenic bacteria in the early stage and suppress the inflammatory response in the late stage to avoid the inflammatory cascade effect and lung tissue damage，indicating that Fuzheng drugs have an important role in maintaining the immune homeostasis of the body after infection.

The mechanism of Er-xian Decoction in regulating lipid metabolism disorders on bilateral ovariectomized rats based on metabolomics study / 药学学报

Studies have shown that women's menopause caused by permanent cessation of ovarian function is closely related to lipid metabolism disorders. Er-xian Decoction has been used in the clinical treatment for gynecological diseases and has a good effect on diseases related to reduced sex hormone function. In this study, metabolomics was performed on bilateral ovariectomized model rats within 12 weeks after modeling to mimic the physiological state of menopausal women in different menopausal stages and Er-xian Decoction dosed model rats. The results of liver oil red O staining sections showed lipid metabolic disorder of bilateral ovariectomized model rats and the regulating effects of Er-xian Decoction. 46 potential biomarkers (6 steroid hormones, 3 sphingolipids, 11 phospholipids and 26 glycerides) in plasma and 32 potential biomarkers (1 steroid hormones, 20 phospholipids and 11 glycerides) in liver were obtained based on lipidomics analysis. Then, we analyzed the differential metabolic pathways and construct the lipid metabolism network significantly regulated by Er-xian Decoction. The results provided valuable information for in-depth understanding of the gradual changes on lipid metabolism disorders under menopausal conditions and the characteristics and mechanisms of compound Er-xian Decoction's regulatory effects. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00000918).

Antipyretic effect of active components of Mahuang Decoction and its correlation with pharmacokinetics in febrile rats / 中国中药杂志

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1β and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.

Effects of Shugan Hewei Decoction and active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats / 中国中药杂志

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.

The effects of antidepressants on inflammatory factors of frontal lobe in depression model rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of antidepressants on frontal lobe inflammatory factors in depressed model rats.Methods Thirty SD rats were randomly divided into 5 groups (n=6):contorl group(Cn),depression group (Dn),citalopram group (Dx),venlafaxine group (Dw) and reboxetine group (Dr).The open field test and sugar consumption test were performed to observe the depression behavior and the changes of FGF-1,TNF-α,IL-1 and CRP were measured in frontal lobe of rats by ELISA.Pearson linear correlation analysis was used to evaluate the correlation between behavioral score and inflammatory factors level in rats.Results (1)Compared with the Cn group,the scores of Dn,Dr,Dw,Dx group were decreased on Open field test and sugar consumption test (P＜0.05).Compared with the Dn group,the scores of the Dx,Dw,Dr group were increased in Open field test and sugar consumption test (P＜0.05).(2)Compared with Cn group,the levels of TNF-α,IL-1 and CRP increased in Dn group and FGF-1 level decreased (P＜0.01).Compared with Dn group,the levels of FGF-1 increased in Dx ((86.54±2.56) ng/L),Dw((79.82±4.89) ng/L)and Dr ((68.50 ± 3.61) ng/L) group,however,the levels of TNF-α decreased in Dx ((150.21±5.65) ng/L),Dw ((161.28±8.80) ng/L),Dr ((175.78±9.67) ng/L) group,and the level of IL-1 also decreased in Dx ((30.87±4.48) ng/L),Dw ((36.65±3.33) ng/L),Dr ((40.14±2.81)ng/L) group,and the levels of CRP also decreased in Dx ((374.88 ± 14.15) ng/L),Dw ((394.21 ± 17.03) ng/L),Dr ((414.34± 10.97)ng/L) (P＜0.01).(3)The behavioral score of each group was positively correlated with of FGF-1 and negatively correlated with TNF-a,IL-1 and CRP (P＜0.05).Conclusion Antidepressants can reduce the level of proinflammatory factors and increase the level of anti-inflammatory factors of frontal lobe in depression model rats,suggesting that antidepressants may play an antidepressant effect by regulating the concentration of inflammatory factors.

Down-regulated expression of duodenal tight junction proteins in model rats with Parkinson's disease / 基础医学与临床

Objective To investigate the alterations of tight junction proteins in duodenal mucosa from 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease(PD) model. Methods Rats were subjected with 6-OHDA in bilateral substantia nigra (SN) as PD model. The location and quantitative detecting techniques inclu-ding immunohisto- chemistry and western blotting were used to determine the expressions and alterations of tight junction proteins (claudin-1, occludin, ZO-1). Results Claudin-1, occludin and ZO-1 were highly expressed in the duodenal mucosa of PD models, where the expressions of occluding (P<0.001) and ZO-1 (P<0.001) were much lower, while the expression of claudin-1 had no alteration. Conclusions The down-regulated expres-sion of occludin and ZO-1 was detected in duodenal mucosa of PD models, which might be related to duodenal ulcer in PD.

Down-regulated expression of duodenal tight junction proteins in model rats with Parkinson's disease / 基础医学与临床

Objective To investigate the alterations of tight junction proteins in duodenal mucosa from 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease(PD) model. Methods Rats were subjected with 6-OHDA in bilateral substantia nigra (SN) as PD model. The location and quantitative detecting techniques inclu-ding immunohisto- chemistry and western blotting were used to determine the expressions and alterations of tight junction proteins (claudin-1, occludin, ZO-1). Results Claudin-1, occludin and ZO-1 were highly expressed in the duodenal mucosa of PD models, where the expressions of occluding (P<0.001) and ZO-1 (P<0.001) were much lower, while the expression of claudin-1 had no alteration. Conclusions The down-regulated expres-sion of occludin and ZO-1 was detected in duodenal mucosa of PD models, which might be related to duodenal ulcer in PD.

Effects of Suanzaoren Decoction on Learning and Memory Ability and Brain Neurotransmitters Content of Senile Insomnia Model Rats / 中国药房

OBJECTIVE:To study the effects of Suanzaoren decoction on learning and memory ability and brain neurotransmit-ters content of senile insomnia model rats. METHODS:Rats were randomly divided into normal group,model group,positive group [Estazolam tablet,2 × 10-3 g/(kg·d)] and Suanzaoren decoction low-dose,middle-dose and high-dose groups [5,10,15 g/(kg·d)],with 10 rats in each group. Except for normal group,those groups were given D-galactose ih on the back+sleep depriva-tion to induce senile insomnia model. 6 weeks after modeling,treatment groups were given relevant medicine intragastrically for one week,and normal group and model group were given normal saline intragastrically. The escape latency,the percentage of swimming time and the time of original platform crossing were observed,and the contents of Glu and GABA in cerebral tissue were determined as well as the contents of IL-1β and 5-HT in hypothalamus. RESULTS:Compared with normal group,escape la-tency of rats prolonged and the contents of IL-1β and 5-HT in hypothalamus decreased,while the percentage of swimming time of original platform quadirant,the time of original platform crossing and the contents of Glu and GABA in cerebral tissue increased (P<0.05). Compared with model group,above index of treatment groups improved significantly,with statistical significance(P<0.05). Compared with positive group,the changes of above index were more significant in Suanzaoren decoction middle-dose and high-dose groups,with statistical significance (P<0.05). CONCLUSIONS:Suanzaoren decoction could markedly enhance the learning and memory ability of senile insomnia model rats,and reduce neurotransmitters content and relieve the delayed neuronal damage which led by Glu and GABA.

Effect of total flavonoids from Nigella glandulifera on inflammation of chronic obstructive pulmonary disease model rats and its mechanism / 中国药学杂志

OBJECTIVE: To investigate the effect of total flavonoids from Nigella glandulifera (TFNG) on inflammation of chronic obstructive pulmonary disease (COPD) model rats and its mechanisms. METHODS: The COPD model rats was established by intratracheal instillation of lipopolysaccha rides (LPS) with inhalation of papain. The model rats were administrated low and high dosage TFNG, water decoction and aminophylline by ig for twenty consecutive days, the model and normal group with distilled water. The general situation of rats were observed and the rats lung tissue were obtained and stained with HE for histopathological examination, inflammatory cells in bronchuoalveolus lavage fluid (BALF) were classified, the levels of inflammatory factors in BALF were measured by ELISA. RESULTS: TFNG (71.5, 286 mg ·kg-1) could improve the general condition of COPD rats, and the pathologic changes of lung tissue were reduced in different degree; the macrophage and neutrophil cells percentage in BALF, and levels of IL-8, TNF-α and NF-κB in BALF were significantly decreased (P < 0.01). CONCLUSION: TFNG can inhibit the inflammation of COPD model rats. The potential mechanism may be related to reducing the reaction of inflammatory cells to LPS, and inhibiting the synthesis and release of inflammatory cytokines.

Comparing studies of silybin metabolism in normal rats and liver injury model rats / 国际中医中药杂志

Objective To research the metabolism and distribution ofsilybin in normal rats and liver injury model rats.Methods The normal rats group and immunity liver injury rat models were fed with the same dose ofsilybin capsule,and HPLC was used to determine the silybin concentration in biological samples in different time.Results The silybin concentration in the normal group in biological samples was higher than the model group at different time.In the normal group,the consequence of silybin concentration in each viscera distribution from top to bottom was liver＞kidneys＞plasma＞heart,while in the model group the fact was kidneys＞heart＞liver＞plasma.Conclusion The difference of metabolism and distribution of silybin in normal rats and liver damage model rats was obvious.

Periventricular Leukomalacia Induced by Prenatal Exposure to Lipopolysaccharide Followed Perinatal Hypoxic Insults: An Animal Model for Perinatally Acquired Encephalopathy / 中国康复理论与实践

@#Objective To establish a new rat model of perinatal brain damage. Methods Wistar rats were randomized into 3 groups: lipopolysaccharide （LPS） plus hypoxia (H) group: 17 d pregnant rats exposure in utero to LPS followed by hypoxia; hypoxia (H)/ ischemia (I) group: postnatal day 7 (P7) pups ligated the right common carotid artery followed by exposure to hypoxia (8% O2 ) for 2 h; control group: P7 pups incised the anteriorl cervical skin only. The footprint analysis, compound muscle action potential (CMAP) and pathological observation were performed after 4 weeks. Results The left limb footprint repeatability of rat in HI and LPS plus H groups was poorer than that in control group （P<0.05）. The hindlimb quadriceps CMAP of rats in HI and LPS plus H groups showed that the wave amplitude was lower than that in control group （P<0.05）. The periventricular cells were irregular, and the periventricular leukomalacia was seen. The morphous of the neurocytes was irregular obviously, part of the nuclear membranes was broken down with the content leakage under transmission electron microscope. Conclusion The animal model for cerebral palsy has established, that mimics more the occurrence of this disease in human.

Acupuncture Therapy for Ischemic Stroke in Model of Rats (review) / 中国康复理论与实践

@#The recent literatures showed that the acupuncture therapy had played a special role in treating ischemic stroke, including the changes of fibrinolysis, amino acid neurotransmitters, active peptides, proteins in the blood, calmodulin, nitric oxide and the synthase, and so on. But the standard of judgments, the manipulations of acupuncture, the selection of acupoints, and the course of treatment remain uncertain.

Advance in Cerebral Ischemic Model with Middle Cerebral Artery Occlusion in Rats(review) / 中国康复理论与实践

@#The middle cerebral artery occlusion(MCAO) in rats remained a focus cerebral ischemic model that is non-incisioned,reliable,as well as the ischemic and refusion time can be controlled,which is widely used since it was created.However,because it is needed complex operations,associatied with many factors,it is difficult to establish.Many scholars have modified the operation,shape of the occlusion line,as well as the variety,narcotic drugs and so on.

Effect of Shugan Jiannao Tiaoyu Tablets on expression of hippocamp C-FOS and C-JUN protein in post-stroke depression rat / 中华中医药杂志

Objective:To study the anti-depression mechanism of Shugan Jiannao Tiaoyu Tablets(SJTT) and provide evidene for clinical application. Methods: Depressive rat model were established by unpredictable stress with raising alone. Model rats were randomly divided into 5 groups, each 12, then each group was administrated through intragastric perfusion daily with the rate of 1.0ml/100g according to their weight before stimulation: fluoxetine group with 0.75 mg/kg, low-dose group of SJTT with 1.8g/kg, high-dose group of SJTT with 3.6g/kg, normal group and model group with 1.0ml/100g of isotonic Na chloride. The whole course lasted for 21 days from the first day of model making to the day of death. The pathologic character of hippocampus was observed by light microscopic examination. The change of cell ultramicrostructure was observed by transmission electron microscope. The expression of C-FOS and C-JUN were detected by immunohistochemistry. Results: SJTT could reduce the neuron damage of hippocam. Compared with model group, the gray scale of immunoreaction positve cells of C-FOS and C-JUN increased in high dose group of SJTT. Conclusion:SJTT can decrease the neuron damage induced by stress in hippacam and had anti-depression effect.

Effect of Chinese medicine Baoganning on lipid and serum leptin of liver fibrosis model rats / 中华中医药杂志

Objective:To discuss the mechanism of Baoganning anti-liver fibrosis.Methods:liver fibrosis rat models were established by complex factors.Automatic biochemical analyzer was used to detect TC、TG and RIA isotope analysis was used to detect serum leptin.To observe the influence of Baoganning on TC、TG and leptin level of liver fibrosis model rats. Results:Compared with the normal group,levels of serum TC,TG decreased apparently in model and every drug groups(P0.05).Conclusion:Baoganning can effectively prevent and treat liver fibrosis in rats,which may be closely related to the improvement of liver function,adjustment of lipid and reduction of serum leptin.

Changes of Blood Lipid,Blood Rheology and Microcirculation of Model Rats of Diabetes Ⅱ with Heart Blood Stasis Syndrome / 中医杂志

Objective To explore the relations among blood lipid,blood rheology and microcirculation of bulbar conjunctiva of model rats of diabetesⅡwith heart blood stasis syndrome.Methods The rats were fed with high fat and caloric feed.Intraperitoneal injection of streptozotocin(STZ)in small dosage was applied to make the model of diabetesⅡ.Then the model of heart blood stasis syndrome was made through introperitoneal injecting dexamethasone and adrenalin.Eight hours after empty stomach,the rats were anaesthetized to measure the microcireulation of bulbar conjunctiva and test the blood lipid and carotid blood rheology.Results The indices of blood lipid,blood rheology and bulbar eonjunetiva microcirculation of model rats were all changed to abnormal,tallying with the changes of cardiovascular complications of diabetes.