This study was aimed to observe effects of different doses of D-galactosamine (D-GalN) plus lipopoly-saccharide (LPS) and blood coagulation changes among rat model of acute liver failure, in order to establish an ideal model of acute liver failure in rats. SD rats were randomly divided into the control group, D-GalN high, medium and low dose groups, with 10 rats in each group. Except the normal group, rats in other groups were injected with D-GalN plus LPS at different doses to induce acute liver failure. The mortality of rats was observed. The liver function and blood coagulation were detected from rat serum at 0 h, 12 h, 24 h, 48 h, and 72 h. HE stain was used in the observa-tion of changes on liver pathological changes. The results showed that the mortality of D-GalN high, medium and low dose groups within 72 h were 60%, 30%, 10%, respectively. There were significant differences on the serum content level of ALT, AST, TBIL, PT, INR, FIB from different dose groups at different time points and the normal group (P<0.05). However, the comparison among D-GalN high, medium and low dose groups showed no statistical difference on ALT and AST; while there were statistical differences on TBIL, PT, INR and FIB (P < 0.05). It was concluded that coagulation index was more stable in the liver failure model. Through observation on the liver function, blood coagulation and pathological morphology, the model of acute liver failure induced with medium dose of D-GalN plus LPS in SD rats at 48 h was more similar to the clinical symptom of acute liver failure. Therefore, the medium dose was the ideal model inducing dose.

Objective To investigate the risk factors associated with gastroparesis syndrome after laparoscopic pancreatoduodenectomy which provide reference for clinical prevention.Methods Ninety cases of laparoscopic pancreatoduodenectomy admitted from August 2013 to December 2016 in Traditional Chinese Medicine Hospital of Guangdong Province were studied retrospectively,57 were male(63.3%),the average age was 54.6 years old.Twenty cases were diagnosed postoparative gastroparesis syndrome(22.2%).To screen out the risk factors,31 independent variables were analyzed by univariate analysis and logistic regression.Results Univariate analysis showed that malnutrition,hypoproteinemia,anemia,pylorus-preserving,extensive lymph nodes dissection,anxiety,high blood sugar before operation,delay of enteral nutrition,abdominal infection and postoperative high blood sugar were associated with postoperative gastroparesis(The value of OR were 3.143,3.587,2.852,2.889,3.231,7.071,2.889,5.359,6.000,6.263,P<0.05).Multivariate Logistic regression analysis showed that extensive lymph nodes dissection,anxiety,pylorus-preserving,abdominal infection,delay of enteral nutrition,hypoproteinemia,postoperative high blood sugar were risk factors of postoperative gastroparesis(The value of OR were 17.574,8.931,6.637,6.461,6.446,5.414,5.200;P<0.05).Conclusion Multiple risk factors can lead to gastroparesis after laparoscopic pancreatoduodenectomy,measures should be taken aimed at these risk factors during perioperative period.

Objective To observe the effectiveness and mechanism of Xiaoyao San (Xiaoyao Powder for Soothing Liver and Relieving Depression) in improving depression-like behavior of rats. Methods Male Wistar rats were randomized into normal group, model group, Xiaoyao San (1.9 g·kg-1·d-1) group, and fluoxetine (2 mg·kg-1·d-1) group. The rats were exposed to chronic unpredictable mild stress ( CUMS) to induce rat depression-like behavior. Field test was performed for the observation of effect of Xiaoyao San on rat depression-like behavior, Luminex liquid chip system was applied to detect the serum cytokines, and the amount and size of rat hepatic sinusoidal endothelial window were examined under electron microscope, and hepatic indoleamine 2, 3-dioxygenase ( IDO) and tryptophan 2, 3 -dioxygenaes ( TDO) expression levels were detected by immunohistochemical and Western blot methods. Results Xiaoyao San showed obvious effect on increasing sugar water consumption, the number of crossing the blocks and erection frequency in rats, decreasing serum levels of tumor necrosis factor alpha ( TNF-α) and interleukin 6 ( IL-6) , increasing the amount of hepatic sinusoidal endothelial window, promoting hepatic sinusoidal endothelial vascularization, and reducing TDO and IDO expression ( P<0.05 or P<0.01). Conclusion Xiaoyao San exerts obvious effect on improving rat depression-like behaviors, and the mechanism is probably related with the decrease of inflammatory factors, inhibition of IDO pathway, and improvement of hepatic sinusoidal endothelial function.

Objective To systemically investigate 1) distribution of endogenous endotoxin (ET) in tissues and circulation; 2) its relationship with shock duration and organ damage; and 3) its possible mechanism after hemorrhagic shock.Methods To further elucidate the intrinsic relationship between endogenous endotoxin translocation and hemorrhagic shock, the present study systematically investigated the distribution of endogenous ET into the liver, lungs, kidneys and circulation, and the relationship between ET levels and the corresponding organ dysfunction with limulus amebocyte lysate (LAL) chromogenic assay following hemorrhagic shock in rats. Results It was found that ET levels in hepatic homogenate markedly increased (P=0.09) 1.5 hours following shock compared with that in the sham group. After resuscitation, ET levels in hepatic, pulmonary and renal tissues were all significantly elevated. The levels kept increasing with the prolonged experimental time, and reached as high as 3.88±0.95 EU (endotoxin unit)/g in the livers, 2.53±1.46 EU/g in the lungs and 2.51±0.89 EU/g in the kidneys 12 hours after shock. ET levels in plasma reached a peak of 1.13±0.42 EU/ml at 1 hour following resuscitation, then rapidly decreased to the sham levels 3 hours following resuscitation. There was a close relationship between endotoxin translocation and shock duration. Correlation analysis further indicated that the changes in glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN) in plasma and angiotensin Ⅰ-converting exzyme (ACE) in pulmonary homogenate were significantly and positively correlated with the ET levels in the liver, kidneys and lungs after hemorrhagic shock. Conclusions Hemorrhagic shock can induce obvious endogenous ET translocation, which is closely related to the shock duration. Although only transient endotoxemia occurs after hemorrhagic shock, ET can massively accumulate in tissues (liver, lungs and kidneys), and may play an important role in the development of shock.

OBJECTIVE: To investigate the effect of bactericidal/permeability-increasing protein(BPI) on the outcome of sepsis in mice and its possible mechanism. METHODS: Sepsis was induced by injection of 2x10(6) colony-formed unit E. coli J5 via the tail vein. BPI of 5 mg/kg or equal volume of normal saline(NS) were injected intravenously at the same time. Endotoxin and TNFalpha levels in serum were assayed using a chromogenic limulus amebocyte lysate test and ELISA respectively. RESULTS: Seventy-two hour survival rate of septic mice was significantly higher in the BPI group (15/18) than in the NS group(8/18, P<0.01). Serum endotoxin levels in the BPI group (1.3+/-0.3 and 0.7+/-0.4 &mgr;g/L) were significantly lower than those in the NS group (3.9+/-0.8 and 2.5+/-0.9 &mgr; g/L, P<0.01) 0.5 and 1 hour following injection of bacteria respectively. The peak levels of serum tumor necrosis factor-alpha(TNFalpha)in the BPI group (1.9+/-0.6 &mgr;g/L) were also markedly lower than those in the NS group (3.8+/-0.8 &mgr;g/L, P<0.01) 1.5 hours following bacterial injection. But there was no significant difference in blood bacterial count between the BPI and NS groups 0.5, 1.5 and 3.0 hours after injection of bacteria. CONCLUSIONS: BPI has a marked protective effect on E. coli sepsis, which might be related to its action against bacterial endotoxin and its inhibition of TNFalpha production in sepsis.

OBJECTIVETo observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression.

METHODSForty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10 ug/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver.

RESULTSThe levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05).

CONCLUSIONSHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.

Animals ; Caspase 3 ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Liver Failure, Acute ; drug therapy ; metabolism ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

Objective To observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression. Methods Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10μg/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver. Results The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05). Conclusion SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.

Objective To explore the protective effect of Xionggui Decoction against cardiac myopathy in a mouse model of heart failure following myocardial infarction(MI)and explore the underlying mechanism.Methods We searched TCMSP,GeneCards,and CTD databases for the targets of active ingredients Xionggui Decoction and heart failure,and the intersecting targets were analyzed with GO and KEGG pathway enrichment analysis using DAVID database.In a mouse model of heart failure following acute MI induced by coronary artery ligation,the cardiac protective effects of 3 g/kg Xionggui Decoction were evaluated by assessing cardiac function,cardiac myopathy and ventricular remodeling of the mice using HE staining,Masson staining,RT-qPCR,and immunohistochemistry.We also tested the effect of Xionggui Decoction at 50 and 100 μg/mL on tert-butylhydrogen peroxide(TBHP)-induced apoptosis of H9C2 cells using CCK8 assay,detection kits for ROS,MDA,SOD,JC-1 and Hoechst 33342/PI staining.Results Network pharmacological analysis identified 62 potential targets of Xionggui Decoction for treatment of heart failure,and the core targets included PTGS2,ESR1,caspase-3,PPARG,HSP90AA1,BCL2,JUN,and GSK3B,which were involved in cell apoptosis and the AGE-RAGE,P53,PI3K-Akt,and VEGF signaling pathways.In the mouse models of heart failure,treatment with Xionggui Decoction significantly alleviated cardiac myopathy and ventricular remodeling,obviously improved heart function of the mice,lowered myocardial expressions of caspase-3 and BAX,and enhanced the expression of BCL2.In H9C2 cells,Xionggui Decoction significantly alleviated TBHP-induced cell apoptosis by inhibiting oxidative stress in the cells.Conclusion Xionggui Decoction can alleviate myocardial injury and improve cardiac function in mice with heart failure following acute MI possibly by inhibiting cardiomyocyte apoptosis induced by oxidative stress.

Objective To observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression. Methods Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10μg/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver. Results The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05). Conclusion SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.

Objective To explore the protective effect of Xionggui Decoction against cardiac myopathy in a mouse model of heart failure following myocardial infarction(MI)and explore the underlying mechanism.Methods We searched TCMSP,GeneCards,and CTD databases for the targets of active ingredients Xionggui Decoction and heart failure,and the intersecting targets were analyzed with GO and KEGG pathway enrichment analysis using DAVID database.In a mouse model of heart failure following acute MI induced by coronary artery ligation,the cardiac protective effects of 3 g/kg Xionggui Decoction were evaluated by assessing cardiac function,cardiac myopathy and ventricular remodeling of the mice using HE staining,Masson staining,RT-qPCR,and immunohistochemistry.We also tested the effect of Xionggui Decoction at 50 and 100 μg/mL on tert-butylhydrogen peroxide(TBHP)-induced apoptosis of H9C2 cells using CCK8 assay,detection kits for ROS,MDA,SOD,JC-1 and Hoechst 33342/PI staining.Results Network pharmacological analysis identified 62 potential targets of Xionggui Decoction for treatment of heart failure,and the core targets included PTGS2,ESR1,caspase-3,PPARG,HSP90AA1,BCL2,JUN,and GSK3B,which were involved in cell apoptosis and the AGE-RAGE,P53,PI3K-Akt,and VEGF signaling pathways.In the mouse models of heart failure,treatment with Xionggui Decoction significantly alleviated cardiac myopathy and ventricular remodeling,obviously improved heart function of the mice,lowered myocardial expressions of caspase-3 and BAX,and enhanced the expression of BCL2.In H9C2 cells,Xionggui Decoction significantly alleviated TBHP-induced cell apoptosis by inhibiting oxidative stress in the cells.Conclusion Xionggui Decoction can alleviate myocardial injury and improve cardiac function in mice with heart failure following acute MI possibly by inhibiting cardiomyocyte apoptosis induced by oxidative stress.