Study On The Mechanism Of Matrine Involved In Renal Dysfunction In Diabetic Rats Through The PI3K/AKT/MTOR Signal Transduction Pathway

Objectives: To estabilish a rat model of diabetic rats and investigate the correlation between the activation of PI3K/AKT/m TOR signal transduction pathway and renal function damage and the intervention effect of matrine.Methods: All well-fed rats were randomly divided into control group(n=5)and experimental groups(n=23).Control group fed basal diet and had free access to water;experimental group fed high-sugar and high-fat diet and free drinking water.Four weeks later,control group were given intraperitoneal injection of 0.1 mol/L sodium citrate solution(10 ml/kg);experimental group were given a one-time intraperitoneal injection of streptozotocin(STZ)(35 mg/kg,i.p.)to establish diabetic rat models.Rats in the experimental group were divided into four groups randomly according to the principle of randomization: model group(n=5),rapamycin group(n=5),matrine low dose group(n=5)and matrine high dose group(n=5).At the 8th week,control group and diabetic model group were fed with saline(1mg/kg).And other groups were given the same dose of drug treatment: rapamycin group were given rapamycin(1mg/kg by gavage),matrine low and high dose group were given matrine(10 mg/kg and 40 mg/kg by gavage,respectively).The treatment lasts for 4 weeks.During the experiment,the control group keep feeding basal diet,experimental group high-sugar,high-fat diet.Results: Compared with the control group,the model group rats had significantly higher level of serum creatinine,urea nitrogen and microalbuminuria,and the difference was statistically significant(P < 0.05);the above indexes of rapamycin group and matrine group rats were significantly restored(P < 0.05),and the effect of the high-dose group was more significant than that of the low-dose group(P < 0.05);compared with the control group,the kidney of the model group rats was significantly better(P < 0.05).The levels of hydroxyproline,PI3 K,AKT and mTOR in the kidney tissue of rats in rapamycin group and matrine group were significantly higher than those in control group(P < 0.05).The above indexes of rapamycin group rats and matrine group were significantly restored(P < 0.05),and the effect of high dose group was more significant than that of low dose group(P < 0.05).Compared with control group,matrix metalloproteinase MMP-2,MMP-9 in kidney tissue of model group rats were significantly higherthan those in control group(P < 0.05).The levels of TIMP1 and TIMP2 were significantly higher in rapamycin group and matrine group than in control group(P < 0.05),and the effects of high dose group were more significant than those of low dose group(P < 0.05).Conclusion: Renal function damage in diabetic rats was related to activation of PI3K/AKT/mTOR signal transduction pathway.Matrine may improve renal injury by inhibiting the above abnormalities.