Exploring The Protective Effect And Mechanism Of Eucommia Extract On Hepatic Ischemia Reperfusion Injury In Rats

Objective:To observe the Protective effect of Eucommia extract on hepatic ischemia reperfusion(IR) injury in rats. And explore it’s mechanism.Methods:A total of 42 male SD rats was randomly divided into 6 groups:Sham-operation(SHAM): Dissecting Duodenal ligament without hepatic blood occlusion; Ischemia-reperfusion group(IR) : occluding the blood of middle lobe and left lobe of liver to build a model of 70% hepatic ischemia for 1h; Ulinastatin group : intraperitoneal injection of Eucommia extract(3000U/kg) 30 min before ischemia. Eucommia-1 group、Eucommia-2 group、Eucommia-3 group:Eucommia preconditioning everyday by oral administration for 10 day before Ischemia(40g/Kg、80g/Kg、160g/Kg).Collecting the samples of blood and liver tissue after reperfusion for 4h, Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), Enzyme-linked immunosorbent adsorption assay(ELISA) was used to detect the plasma tumor necrosis factor alpha(TNF-α) and interleukin 1(IL-1). Xanthine oxidase method was used to detect the liver tissue SOD,Thiobarbituric acid method was used to detect the MDA. and observe hepatic histopathological changes.Results:(1)Liver tissue pathology: The IR group showed remarkable edema of hepatocytes, narrowing of liver sinusoid, necrosis of the liver cells, inflammatory cell infiltration and disorder of hepatic plate structure;The Eucommia preconditioning groups showed the necrosis of hepatocytes and the inflammatory cell infiltration was significantly decreased, The damage of pathology was lightened with the increasing dose of Eucommia.(2)Serum liver function: The level of ALT and AST in the Eucommia preconditioning groups were significantly lower than in the IR group(P<0.05); Comparing with Eucommia preconditioning groups,the levels of ALT and AST in Ulinastatin group were significantly lower(P<0.05); the levels of ALT and AST in the Eucommia-2 group and the Eucommia-3 group were lower than in the Eucommia-1 group(P<0.05).(3) Liver homogenate SOD: The level of SOD activity in the IR group was lower than other groups with Eucommia preconditioning(P<0.05);The level of SOD activity in the Eucommia-1 group was lower than in the Eucommia-2 group and the Eucommia-3 group(P<0.05);The level of SOD activity in the Ulinastatin group was higher than in the Eucommia-1 group、the Eucommia-2 group and the Eucommia-3 group(P<0.05).(4) Liver homogenate MDA: The level of MDA in the IR group was higher than other groups with Eucommia preconditioning(P<0.05);The level of MDA in Eucommia-1 group was higher than in the Eucommia-2 group and the Eucommia-3 group(P<0.05);The level of MDA in Ulinastatin group was lower than in the Eucommia-1 group、the Eucommia-2 group and the Eucommia-3 group(P<0.05).(5)Liver homogenate cytokines: The level of cytokines in the IR group was higher than other groups with Eucommia preconditioning(P<0.05);The level of cytokines in Eucommia-1 group was higher than in the Eucommia-2 group and rhe Eucommia-3 group(P<0.05);The level of cytokines in Ulinastatin group was lower than in the Eucommia-1 group、the Eucommia-2 group and the Eucommia-3 group(P<0.05).(6)Liver Serum HMGB1: The level of HMGB1 in the IR group was higher than other groups with Eucommia preconditioning(P<0.05);The level of HMGB1 in Eucommia-1 group was higher than in the Eucommia-2 group and the Eucommia-3 group(P<0.05);The level of cytokines in Ulinastatin group was lower than in the Eucommia-1 group、the Eucommia-2 group and the Eucommia-3 group(P<0.05).Conclusion:1.Eucommia extract has a protective effect against hepatic ischemia reperfusion injury in rats,and reduces ALT and AST levels,and lessens Pathological injury. 2.Eucommia extract lessens the IR injury through inhibiting the inflammatory reaction and peroxidation. It is mechanism problably relates to the inhibition of HMGB1.3.The protective effects of high-dose Eucommia and Medium dose Eucommia(160g/kg、80g/kg) are better than that of low-dose Eucommia(40g/Kg).