Preliminary Study Of Xinjiangtang Granule On Glucolipid Metabolism And Liver And Kidney Protection In Type 2 Diabetic Rats

Objective:Xinjiangtang Granule is self-developed products. T2 DM rats model was induced by high-fat diet and intraperitoneal injection of STZ to investigate preliminary study of Xinjiangtang granule on glucolipid metabolism and liver and kidney protection in type 2 diabetic rats.Methods:Fifty male SD rats were randomly divided into normal control group(8 rats feed with normal diet) and experimental group which were fed by high-fat-diet for 4 weeks and then peritoneal injection of streptozotocin(STZ, 40mg?kg-1) to induce T2 DM rats.After the success of the modeling, the model rats were randomly subdivided into T2 DM model group, positive control group(metformin 0.15g·kg-1), Xinjiangtang granule group with high dose and low dose(12.64 g·kg-1, 6.32 g·kg-1). Rats were intragastric administered once daily for eight weeks. After treatment for 8 weeks:(1)Weigh the weight, food intake and water intake of rats; detect FBG with glucose oxidase method; detect FINS with radioimmunological method; detect HOMA-IR with homeostasis model method; detect HbA1 c, the content of hepatic glycogen, TC,TG and the activity of HK, PFK, PK, G-6-PDH with colorimetric method; detect HDL-C and LDL-C with selective precipitation method.(2)Detect PEPCK, G6 Pase and FOXO1 mRNA of liver with Real-Time PCR method; detect FOXO1 protein with western blotting method.(3)Detect serum ALT, AST, ALP with microplate method;detect γ-GT, GSH-PX and CAT of liver with colorimetric method; detect SOD of liverwith hydroxylamine method; detect MDA of liver with thiobarbituric acid method;detect liver with HE staining method.(4)Detect BUN with diacetyl monoxime method;detect Scr with sarcosine oxidase method; detect GSH-PX and CAT of kidney with colorimetric method; detect SOD of kidney with hydroxylamine method; detect MDA of kidney with thiobarbituric acid method; detect AGEs with ELISA method; detect PAI-1、TGF-β1、RAGE mRNA of kidney with Real-Time PCR method; detect kidney with HE staining method.Results:(1)Glucolipid metabolism index showed: Comparing with model group,Xinjiangtang granule high dose and low dose groups can decline food intake and water intake, FBG, HOMA-IR, serum of TC, TG and LDL-C(P<0.05, P<0.01),increase weight, the content of hepatic glycogen, HDL-C and the activity of HK,PFK, PK, G-6-PDH(P<0.05, P<0.01), Xinjiangtang granule high dose group can decline FINS and HbA1c(P<0.05, P<0.01), Xinjiangtang granule low dose group can decline TC and TG(P<0.05, P<0.01), increase HDL-C(P<0.05, P<0.01), Xinjiangtang granule low dose group can decline FINS and HbA1 c, Xinjiangtang granule high dose group can decline TC and TG, but they have no statistical significance(P>0.05).(2)Gluconeogenesis index showed: Comparing with model group, Xinjiangtang granule high dose and low dose groups can decline PEPCK, G6 Pase, FOXO1 mRNA and FOXO1 protein of liver(P<0.05, P<0.01).(3)liver amage index showed: Comparing with model group, Xinjiangtang granule high dose and low dose groups can decline ALT, AST and γ-GT,MDA(P<0.05, P<0.01), increase the activity of SOD, GSH-Px and CAT(P<0.05,P<0.01), Xinjiangtang granule low dose group can decline ALP(P<0.01),Xinjiangtang granule high dose and low dose groups can decline fatty degeneration and vacuoles degeneration, most of liver cells are normal and they arrange the rules.Xinjiangtang granule high dose group can decline ALP, but it has no statistical significance(P>0.05).(4)kidney damage index showed: Comparing with model group, Xinjiangtang granule high dose and low dose groups can decline BUN, Scr, MDA, serum of AGEs,the express of PAI-1 and TGF-β1 mRNA(P<0.05, P<0.01), increase the activity of SOD and CAT(P<0.05, P<0.01), Xinjiangtang granule low dose group can decline GSH-Px(P<0.01), Xinjiangtang granule high dose and low dose groups can decline mesangial cell and stroma, improve loose and vacuolized kidney tubules cells.Glomerulus was clear and saccule wall was smooth. Xinjiangtang granule high dose group can increase GSH-Px, but it has no statistical significance(P>0.05).Conclusions:These results demonstrated that Xinjiangtang granule could remarkably improve condition of type 2 diabetic rats. And the regulatory mechanism may be associated with that inhibiting PEPCK, G6 Pase, FOXO1 mRNA and FOXO1 protein level,increasing the activity of HK、PFK 、PK、G-6-PDH, promoting the synthesis of hepatic glycogen, improving liver and kidney function and blood fat metabolism,weakening oxidative stress of liver and kidney, improving insulin resistance, then inhibiting AGEs, RAGE and TGF-β1, PAI-1mRNA expression, eventually decreasing the level of FBG and HbA1 c of type 2 diabetic rats.