| Study one Establish the liver failure model with IETMObjectives:Use different dose of D-gal to establish the model of IETM and choose the dose which accordance with the change of liver failure best.Methods:86rats wre randomly divided into five groups:normal group and low、middle、high and ultra-dose group of D-gal.nomal group contain6rats,other groups contain20respectively; the low、middle、high and ultra-dose group of D-gal wre intraperitoneal inject different dose of D-galactosamine to establish the model of IETM,rats in normal group were intraperitoneal inject the same amount of saline.24h48h after modeling, the death of each group, the liver function(ALT、AST)、liver and intestinal histopathology、endotoxin in portal vein were inspectedRrsults:General state:All rats in normal group were activities normal and survived.states of rats in model group of D-gal were aggravated with the dose of D-gal increase, the most obvious was ultra-dose group.The death rate of rats in low、middle、high and ultra-dose group of D-gal was20%、20%、30%、40%respectively, due to the small sample, it is not used for statistical analysis.Liver function:Compared with normal group,the ALT、AST of rats in model group of D-gal were higher,the differences was statistically significant (P<0.01). The ALT、AST of rats in model group of D-gal were increased with the dose of D-gal increasing, the most obvious was ultra-dose group,the differences was statistically significant (p<0.05;p<0.01). Results of liver pathology:Compared with normal group,the liver tissue damage of rats in model group of D-gal were significantly increased,the differences was statistically significant (P<0.01). liver tissue damage of rats in low、middle、high and ultra-dose group of D-gal were increased with the dose of D-gal increasing, the most obvious was ultra-dose group. the differences was not statistically significant (P>0.05).Results of colon tissue pathology:Compared with normal group,the colon tissue damage of rats in model group of D-gal were significantly increased,the differences was statistically significant (P<0.01). colon tissue damage of rats in low、middle、high and ultra-dose group of D-gal were increased with the dose of D-gal increasing, the most obvious was ultra-dose group, the differences was not statistically significant (P>0.05) at24h, the differences between low、middle groups and ultra-dose group were statistically significant(p<0.05;p<0.01) at48h.Endotoxin in portal vein:Compared with normal group, endotoxin in portal vein of rats in model group of D-gal were higher,the differences was statistically significant (P<0.01). endotoxin of rats in low、middle、 high and ultra-dose group of D-gal were increased with the dose of D-gal increasing, the most obvious was ultra-dose group. the differences was statistically significant (p<0.05;p<0.01).Conclussion:1. IETM model could be induce by inject D-gal intraperitonealy.2. Intraperitoneal inject D-gal at the dose of1.8g/kg not only well Simulate related changes caused by IETM but easy to observe the Intervention role of drug. Study two Intervention role of Wen yang jie du hua yu prescription on liver failure rats with IETMObjectives:To explore the intervention role of different dose of Wen yang jie du hua yu prescription on liver failure rats with IETM and possible mechanism.Methods:80rats were randomly divided into four groups:model group、low dose of Wen yang jie du hua yu prescription group(low dose group)、 middle dose of Wen yang jie du hua yu prescription group(middle dose group)、high dose of Wen yang jie du hua yu prescription group(high dose group),each group contain20rats.Five days before modeling,rats in low、 middle and high dose group were gavaged with different dose of Wen yang jie du hua yu prescription,rats in model group were gavaged with equal dose of saline,every12h till put to death.24h48h after modeling, the rate of death、liver function(ALT、AST)、liver and intestinal histopathology、endotoxin in portal vein were inspected.Rrsults:Death rate:death rate of model group was25%,death rate of low、 middle and high group was descend with the dose of wen yang jie du hua yu prescription increasing,the death rate were20%、20%and10%respectively, due to the small sample, it is not used for statistical analysis.Liver function:Compared with model group,the ALT、AST of rats in low、middle and high dose group of wen yang jie du hua yu prescription were descent,the differences between model and high dose group were statistically significant (P<0.01).Results of liver pathology:Compared with model group,the liver tissue damage of rats in low、middle and high dose group of wen yang jie du hua yu prescription were significantly decreased,the differences between model and high dose group were statistically significant (P <0.05).Results of colon tissue pathology:Compared with model group,the colon tissue damage of rats in low、middle and high dose group of wen yang jie du hua yu prescription were significantly decreased, the differences between model and high dose group were statistically significant (P<0.05).Endotoxin in portal vein:Compared with model group, endotoxin in portal vein of rats in low、middle and high dose group of wen yang jie du hua yu prescription were lower,the differences between model and high dose group were statistically significant (p<0.05;p<0.01).Conclussion:1.Wen yang jie du hua yu prescription have intervention role on liver function and pathology of rats with IETM of liver failure,especially the high dose exert a higher role.2.possible mechanism of Wen yang jie du hua yu prescription anti-liver failure might be it could reduce the colon tissue pathological changes and the absorption of endotoxin. Study three The effect of wen yang jie du hua yu prescription on tight connection of rats with IETMObjectiv:To investigate the effect of wen yang jie du hua yu prescription on tight connection of rats with intestinal endotoxemia(IETM) and explore its potential mechanism of anti-hepatic failure.Method:85rats were randomly divided into four groups:normal group、model group、wen yang jie du hua yu prescription group(experimental group) and glutamine group(control group),the normal group contain10rats,other group contain25rats respectively. The model of hepatic failure intestinal endotoxemia was established by intraperitoneal injection of D-galactosamine. normal group were put to death twenty-four hours after intraperitoneal injection of saline. respectively select6、7、7rats from model group、experimental group and control group and put them to death at24h,48h,72h after modeling,the liver function, intestinal histopathology,endotoxin,expression of occlusal protein(occludin) and myosin light chain kinase(MLCK) in intestinal epithelial were inspected.Rrsults:General state:Compared with nomal group,clinic score of rats in model group was lower,the differences was statistically significant (p<0.01). Compared with nomal group, clinic score of rats in experimental and control group were higher, the differences was statistically significant (p<0.05); the differences between experimental and control group were not statistically significant (P>0.05).the death rate in model、experimental and control group were28%、16%and20%respenctive.Liver function:Compared with nomal group,the ALT、AST of rats in model group was increased,the differences were statistically significant (P<0.01). Compared with model group,the ALT、AST of rats in experimental and control group were decreased,the differences were statistically significant (p<0.05;p<0.01). the differences between experimental and control group were not statistically significant (P>0.05).Results of colon tissue pathology:Compared with nomal group,the colon tissue damage of rats in model group were increased, the differences was statistically significant (P<0.01). Compared with model group,the colon tissue damage of rats in experimental and control group were decreased, the differences was not statistically significant (P>0.05) at24h, the differences were statistically significant (p<0.05) at48h and72h; the differences between experimental and control group were not statistically significant (P>0.05).Endotoxin:Compared with nomal group, endotoxin in portal vein and colon were higher in model group, the differences was statistically significant (P<0.01). Compared with model group, endotoxin in portal vein and colon were lower in experimental and control group, the differences were statistically significant (p<0.05;p<0.01), the differences between experimental and control group were not statistically significant (P>0.05).Expression of occludin:Compared with nomal group, expression of occludin were lower in model group, the differences was statistically significant (P<0.01). Compared with model group, expression of occludin were higher in experimental and control group, the differences was not statistically significant (P>0.05) at24h, the differences were statistically significant (p<0.05) at48h and72h; expression of occludin in experimental were lower than control group,the differences between experimental and control group were not statistically significant (P>0.05).Expression of MLCK:Compared with nomal group, expression of MLCK were higher in model group, the differences was statistically significant(p<0.05;p<0.01). Compared with model group, expression of MLCK were lower in experimental and control group, the differences was not statistically significant (P>0.05) at24h, the differences were statistically significant (p<0.05) at48h and72h; expression of MLCK in experimental were lower than control group,the differences between experimental and control group were not statistically significant (P>0.05).Conclussion:1.Wen yang jie du hua yu prescription can strengthen the tight connection of intestinal tissue of rats with IETM by raised the expression of occludin in colon mucosa and inhibition the expression of MLCK in colonic mucosa.2.Possible mechanisms of Wen yang jie du hua yu prescription anti-hepatic liver failure might be it could decrease the amount of endotoxin absorbed by strengthen the tight connection of intestinal tissue of rats with IETM. |
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