Effect of Qilee Tongluo Formula on Autophagy and Renal Function in Rats with Diabetic Nephropathy by Regula-ting PI3K/Akt/TSC2/mTOR Pathway
Objective:To observe the interventional effects of Astragalus Tongluo Formula on autophagy and renal function and the regulation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/tuberous sclerosis complex 2(TSC2)/mammalian rapamycin signalling in diabetic nephropathy rats,and to study the protective mechanism of Astragalus Tongluo For-mula against diabetic nephropathy.METHODS:85rats were randomly selected 15as normal group,and the rest were fed with high sugar and high fat chow combined with small-dose streptozotocin(STZ)intraperitoneally to induce diabetic nephropathy rat mod-el.The rats were randomly divided into the model group,the low,medium and high dose groups(1.215,2.43and 4.86g/kg)of Astragalus Hirudinea Tongluo Formula and the irbesartan group(0.0135g/kg),with 10rats in each group.Each group was ga-vaged with the corresponding drugs or saline once/d for 8w.The histopathology of blood,urine and kidney and the expression of related proteins were detected.Results:Compared with the normal group,the quantitative 24h urine protein(UTP),serum total cholesterol(TC)and triglyceride(TG)levels were increased in the model group(P<0.05);compared with the model group,Astragali Hirudinea and Tongluo Formula could reduce 24h urine protein(UTP),the blood creatinine(Scr),urea nitrogen(BUN),fasting blood glucose(FBG),total cholesterol(TC)and triglyceride(TG)in rats with diabetic nephropathy.and 24h urine protein quantification(UTP)(P<0.05,P<0.01),attenuate renal pathological changes,reduce p-PI3k,p-Akt,p-TSC2,p-mTOR protein expression,and the difference between Astragalus Tongluo low,medium,and high dosage groups and Irbesartan group was not statistically significant(P>0.05).In addition,Astragalus Tongluo Formula inhibited the expression of p-PI3K,p-Akt,p-TSC2,and p-mTOR in renal tissues of DN rats,which in turn increased the expression level of LC3B,an autophagy marker protein,and the ratio of LC3B-Ⅱ/LC3B-Ⅰ.CONCLUSION:Astragalus Tongluo Formula can inhibit the ele-vation of 24h UTP and improve the renal pathological changes in rats with diabetic nephropathy,and the mechanism of the above nephroprotective effects may be related to its inhibition of the PI3K/Akt//TSC2/mTOR signalling pathway,which then promotes renal autophagy.