Study Of Therapeutical Effects And Mechanisms Of Muguakusang Tablets In Type 2 Diabetic Rats

Objective:To investigate the therapeutic effects and potential mechanisms of MuGuaKuSang tables?MGKS?in type 2 diabetes mellitus?T2DM?rats induced by high fat diets?HFD?and streptozotocin?STZ?.Methods:100 male SD rats were numbered according to the body weight,10 of them were randomly selected as the normal control rats?Control?,which were fed with normal diet.The other 90 rats were fed with HFD for 4 weeks,and then a single intraperitoneal injection of a prepared solution of STZ(45mg·kg^-11 suspended in 0.1 mol·L^-1 citrate buffer at pH=4.5)was applied to induce diabetic models.If volume of fasting blood glucose?FBG?between 11.0mmol·L^-11 and 29.0 mmol·L^-1 after 72 hours of STZ injection,the diabetic models were successful.Symptoms and body weight and FBG were monitored weekly.On the 26th day of administration,the rats'urine volume,water intake,and food intake for 24 hours were recorded.On the 28th day of administration,fasting serum insulin?FINS?was measured by Elisa method,and the insulin resistance index?IRI?was calculated.On the 28th day of administration,the oral glucose tolerance test?OGTT?was performed.After 4 weeks of treatment,the rats were fasted overnight,and blood was then collected from the abdominal aorta,the rats were executed,and the following indicators were measured:1.The pancreas and liver tissue of each group were removed and fixed for pathological observation.2.We also measured the serum catalase?CAT?,superoxide dismutase?SOD?,malondialdehyde?MDA?and nitric oxide?NO?,low-density lipoprotein cholesterol?LDLC?,high-density lipoprotein cholesterol?HDLC?and triglyceride?TG?,total cholesterol?TC?,alanine aminotransferase?ALT?,aspartate aminotransferase?AST?,creatinine?Cr?,urea nitrogen?BUN?and creatine kinase?CK?.3.The protein expression of AMPK-?,IRS-2,and GLUT-4 in the liver tissue was analyzed by Western-Blot.4.The mRNA expression of AMPK-?,IRS-2,and GLUT-4 in the liver tissue was analyzed by RT-PCR.Results:1.To a certain extent,the typical symptoms of T2DM,such as polyphagia,polydipsia,polyuria and emaciation of rats were relieved by MGKS.2.Compared to the model group,the FBG and IRI levels of diabetic rats in the MGKS groups were significantly lower.OGTT results showed that the glucose and the area underneath glucose tolerance curves at 0h,0.5h,1h,and 2h of the MGKS groups are reduced.3.HE staining showed that MGKS protected the pathological changes of the pancreatic and liver tissue of the diabetics.4.MGKS increased the CAT?SOD activity,and it lowered serum MDA and NO levels?P?0.05 or P?0.01?.5.MGKS increased the serum content of HDLC,and it lowered serum TG?TC and LDLC levels?P?0.05 or P?0.01?.6.The serum ALT and AST activity of diabetic rats were significantly reduced,serum Cr and BUN levels were significantly decreased in the MGKS_H and MGKS_M groups?P<0.05 or P<0.01?;The activity of serum CK in the MGKS_M group and MGKS_L group were significantly reduced?P<0.05 or P<0.01?.It prompts that MGKS can protect important viscera from injuring of diabetic.7.The protein and mRNA expression of AMPK-?,IRS-2 and GLUT-4 in the liver tissue were up-regulated by MGKS.Conclusion:The study showed that MGKS can improve the typical symptoms of T2DM,regulate the glucose&lipid metabolism,also can improve insulin resistance and oxidative stress levels.What's more,it can protect and regulate important viscera from injuring of diabetic.The possible mechanism may be associated with the IRS-AMPK-GLUT-4 signaling pathway.