Effect Of Tianxingjian Shenwei Granule On Insulin Resistance In Type 2 Diabetic Rats And Its Mechanism

Objective:Type 2 diabetic insulin resistance rat model was created by high-fat diet combined with tail vein injection of streptozotocin,and the effects of Tianxingjian Shenwei granule on glucose and lipid metabolism,oxidative stress injury,inflammatory factors and IRS/PI3K/AKT signaling pathway in liver of model rats were observed.To investigate the effect and mechanism of Tianxingjian Shenwei granule on insulin resistance in type 2 diabetic rats.Method:IR model of type 2 diabetic SD rats was established by feeding high-fat diet for 4 weeks combined with tail vein injection of STZ(35mg/Kg).Fifty rats with successful modeling were randomly divided into model group,metformin group and high,medium and low dose groups of Tianxingjian Shenwei granule,with 10 rats in each group;Another 10 normal SD rats of the same week old were selected as the blank group.The rats in each group were given corresponding water and drug intervention for 4 weeks.The changes of body weight in each group before and after intervention were observed,and the changes of FBG level before and after intervention were detected by glucose meter.After 4 weeks of intervention,OGTT test was performed and area AUC under glucose tolerance curve was calculated.Four weeks after intervention,abdominal aorta was dissected and the blood was collected by negative pressure vacuum.Serum Fins level and insulin resistance index HOMA-IR were detected.The contents of TC,TG,HDL-C and LDL-C in serum of rats were detected.The levels of SOD,MDA and GSH-Px in serum of rats were detected.Serum levels of inflammatory factors IL-6,TNF-α and adiponectin were detected.The levels of AST,ALT,Scr and BUN in liver function and renal function were detected.HE staining of liver tissue was performed to observe the pathological changes of rat liver.To further clarify the mechanism of Tianxingjian Shenwei granule on improving HEPATIC IR of T2 DM,the protein expression levels of IRS-1,PI3 K,p-PI3 K,AKT and p-AKT in liver tissues were detected by western blot,and the m RNA expressions of IRS-1,PI3 K and AKT in liver tissues of rats in each group were detected by real-time quantitative PCR.Results:1.Compared with the blank group,FBG of the model group increased significantly,and OGTT test was abnormal.The blood glucose in the model group increased significantly at 0min,the peak of blood glucose was delayed,and the blood glucose did not fall back significantly at 120 min,and the blood glucose and AUC at each time point increased significantly,indicating that the model group showed a significant decrease in glucose tolerance.However,Tianxingjian Shenwei granule could reduce the level of FBG,blood glucose and AUC at each time point of OGTT test.Compared with the blank group,Fins,HOMA-IR,TC and TG were increased in model group,while The levels of Fins,HOMA-IR,TC and TG were decreased by Tianxingjian Shenwei granule.Among them,Tianxingjian Shenwei granule has the best effect in high dose.2.Compared with blank group,the contents of SOD and GSH-Px in model group were significantly decreased,while the content of MDA was significantly increased,indicating that there was oxidative stress injury in model group.However,Tianxingjian Shenwei granule could increase the content of SOD and GSH-Px and reduce the content of MDA,indicating that Tianxingjian Shenwei granule played an important role in improving oxidative stress injury.Compared with the blank group,the levels of IL-6 and TNF-α in model group were significantly increased,indicating that there was an inflammatory response in model group,while The levels of IL-6 and TNF-α in Tianxingjian Shenwei granule could be reduced,indicating that Tianxingjian Shenwei granule could reduce the inflammatory response in type2 diabetic rats.Tianxingjian Shenwei granule had the best effect in improving oxidative stress and inflammatory factors at high dose.3.Compared with blank group,AST,ALT,Scr and BUN in model group were significantly increased.In the model group,the arrangement of hepatocyte plates is irregular,the cytoplasmic staining is uneven,cytoplasmic fusion swelling and nuclear pyknosis can be seen,the hepatocytes along the peripheral blood vessels show moderate steatosis,and a small amount of inflammatory cell infiltration can be seen.Tianxingjian Shenwei granule can reduce AST,ALT,Scr and BUN levels in rats,and improve the pathological damage of liver tissue in different degrees,among which Tianxingjian Shenwei granule have the best effect in high dose.4.Western blot and Real time-PCR detection : Compared with blank group,the relative expression levels of IRS-1,p-PI3 K,PI3k,p-AKT and AKT proteins in model group were decreased.Tianxingjian Shenwei granule can increase the protein expression levels of IRS-1,p-PI3 K,p-AKT and AKT in rats.Compared with blank group,the m RNA levels of IRS-1,PI3 K and AKT were significantly decreased in model group,and Tianxingjian Shenwei granule could increase the m RNA levels of IRS-1,PI3 K and AKT in rats.Conclusion:1.The high dose of Tianxingjian Shenwei granule can improve glucose and lipid metabolism disorder,glucose tolerance and insulin sensitivity in type 2 diabetic rats.2.The high dose of Tianxingjian Shenwei granule can improve oxidative stress injury and inflammatory response in type 2 diabetic rats.3.Tianxingjian Shenwei granule can protect the liver and kidney function of type 2 diabetic rats and reduce the pathological damage of liver.4.Tianxingjian Shenwei granule regulate IRS/PI3K/AKT signaling pathway,which may be one of the mechanisms of Tianxingjian Shenwei granule to improve glucose and lipid metabolism disorder and insulin resistance in type 2 diabetic rats.