| Objective: To observe the effects of Modified Xiao-Xian-Xiong Decoction(MXD)on the general condition,body weight,fasting blood glucose(FBG),oral glucose tolerance test(OGTT),pathological changes of liver tissue,liver injury related indicators,serum inflammatory factors,liver tissue oxidative stress response and Nrf2/HO-1 pathway protein expression of type 2 diabetes rats induced by high glucose and high-fat diet combined with streptozotocin.To explore the protective effect of MXD on liver injury in T2 DM rats and clarify its possible mechanism,so as to provide some experimental basis for its clinical application in preventing and treating liver injury in diabetesMethods: 60 SPF grade male Wistar rats were randomly divided into two groups.The control group(n=10)was fed with standard feed;The experimental group(n=50)was given a high-fat and high-sugar diet.Four weeks later,rats in the experimental group were injected intraperitoneally with STZ solution(30 mg/kg/d)with a concentration of 1%,once within 48 hours,twice in total;The rats in the control group were intraperitoneally injected with the same volume of sodium citrate buffer.Select 40 successful T2 DM model rats were randomly divided into model group,metformin group(200 mg/kg/d)and low and high dose MXD group(630,1260 mg/kg/d)according to the FBG level,intragastric administration,10 in each group;At the same time,rats in the control group and model group were gavage with equal volume of distilled water for a total of 4 weeks.The overall situation of each group of mice was closely monitored during the trial,and the body mass and fasting blood glucose(FBG)level of rats in each group were recorded before and after the first,second,third and fourth weeks of administration;After the last administration,OGTT was performed;The pathological changes of liver tissue were observed by hematoxylin eosin(HE)staining;The contents of ALT and AST in serum of rats were detected by automatic biochemical analyzer;Detection of IL-1β,IL-6 and TNF-α content in rat serum by enzyme-linked immunosorbent assay(ELISA);The indexes of SOD,GSH and MDA in rat liver tissue were detected by spectrophotometer;The expression of Nrf2 and HO-1 protein in rat liver tissue was detected by Western blot.Result: After 4 weeks of intragastric administration,compared with the control group,the body mass of the model group rats was significantly reduced(P<0.01),while the FBG level,serum ALT and AST levels were significantly increased(P<0.01);The structural arrangement of liver tissue is loose and irregular,with edema,hyperemia,and severe infiltration of inflammatory cells;the level of IL-1β,IL-6 and TNF-α in serum was significantly increased(P<0.01),the level of MDA in liver tissue was significantly increased(P<0.01),while the activity of SOD,the level of GSH,and the expression of Nrf2 and HO-1 protein in liver tissue were significantly decreased(P<0.01).Compared with the model group,there was no significant change in body mass in the low and high dose MXD groups(P>0.05),while FBG levels,serum ALT and AST activities were significantly decreased(P<0.01);In the low and high dose MXD groups,the hepatocytes of the rats were neatly arranged,their morphology recovered well,and the infiltration of inflammatory cells basically disappeared;the level of IL-1β,IL-6 and TNF-α in serum was decreased significantly(P<0.01),the level of MDA in liver tissue decreased significantly(P<0.05 or P<0.01),and the activity of SOD,the level of GSH,and the expression of Nrf2 and HO-1 protein in liver tissue increased significantly(P<0.05 or P<0.01).Conclusion: MXD can protect the liver injury of T2 DM rats induced by high-sugar and high-fat diet combined with STZ.The effect is related to anti-inflammatory and activation of Nrf2/HO-1 signal pathway and inhibition of oxidative stress.The in-depth molecular mechanism remains to be further studied. |
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