Study On The Protective Effect Of Tongxinluo On Kidney Of STZ Diabetic Rats Based On PI3K/mTOR Pathway

ObjectiveTo investigate the protective effect of Tongxinluo on the kidneys of diabetic rats based on PI3K/mTOR pathway,and provide a new treatment direction for the prevention and treatment of early diabetic nephropathy.MethodsThe 40 healthy male SD rats were randomly divided into the normal control group(CON group)12,and the model group was 28.In the model group,the diabetic model was made by injecting Streptozotocin(STZ)55mg/kg on an empty stomach,and the blood glucose was greater than 16.7mmol/L after 72 hours.The 24 rats with successful model were randomly divided into diabetes group(DM group)and tongxinluo group(TXL group),with 12 patients in each group.After 8 weeks of administration,the electronic balance weighed the weight and kidney weight of rats.Full automatic biochemical analyzer to detect urea nitrogen(blood urea nitrogen,BUN),serum creatinine clearance rate(creatinine clearance rate,Ccr),serum creatinine,(serum creatinine,Scr),24-hour urine trace albumin(24 hour urine microalbuminuria,mALB),fasting glucose,fasting plasma glucose,FBG);The ultrastructure of renal tissue was observed by electron microscope.Immunohistochemistry was used to detect the expression of TGF-beta 1 and CTGF cytokines.Western blot method was used to detect PI3 K,p-PI3 K,mTOR and p-mTOR.Results1.General situation: Compared with normal rats,DM group showed obvious weight loss of body type,and more drink,more food,more urine,typical symptoms of more than one less.Compared with the normal control group,the rats in the model group and the experimental group were significantly emaciated with apathy,decreased activity,delayed movement,and easy infection.The general state of the Tongxinluo group was better than that of the diabetic group.During the experiment,4 rats with blood glucose lower than 16.7 mmol/L after STZ injection and 2 rats that died during feeding were discarded from the experiment.2.Compared with CON group,DM group relative kidney weight,Scr,BUN,24 hours urine albumin,FBG higher,there was significant difference(P < 0.01),and body weight,Ccr was low,there were differences(P < 0.05).Compared with DM group,TXL group,Ccr weight is higher,there was significant difference(P < 0.01),while the Scr is slightly lower,with the difference(P < 0.05),BUN,24 hours urinary albumin,low FBG,there was significant difference(P < 0.01).3.Ultrastructure of renal tissue under electron microscope: The rats in the CON group were uniformly distributed glomerular basement membranes,no expanded mesangial matrix,and neat foot processes.In the DM group,there were obvious basement membranes with uneven width and width distribution,obvious expanded matrix,and miscellaneous foot processes.The podocytes were swollen and had large vacuoles.The lesions in the TXL group were less than those in the DM group.4.The protein expression of TGF-β1 and CTGF: compared with group CON,the expression levels of TGF-β1 and CTGF in DM group increased,and compared with DM group,the expression levels of TGF-β1 and CTGF in TXL group were significantly reduced.5.Western Blot test results: compared with CON group,there was no significant difference between groups in total protein PI3 K and mTOR(P > 0.05);compared with CON group,the expression of DM in the group of p-PI3 K and p-mTOR increased significantly(P < 0.01),showed that PI3K/mTOR signaling pathway is activated;compared with DM group,the expression of p-PI3 K and p-mTOR was higher than DM group decreased,the difference was statistically significant(P < 0.01).Conclusions1.Tongxinluo on diabetic rat kidney tissue has a protective effect,can reduce kidney damage and improve renal function.2.Tongxinluo reduce renal TGF-β1 and CTGF protein expression decreased,reducing DN of renal fibrosis.3.Tongxinluo may protect diabetic kidney tissue through inhibiting PI3 K / mTOR pathway.