TEA POLYPHENOLS IMPROVE KIDNEY PODOCYTE INJURY IN AGED TYPE 2 DIABETES RATS VIA MTOR/PINK1 MITOPHAGY SIGNALING PATHWAY
Objective To explore whether tea polyphenols(TP)improve kidney podocyte injury via mTOR/PINK1 mitophagy signaling pathway in aged type 2 diabetes model rats(T2DM).Methods Forty rats were adaptively fed for 1 week,then randomly divided into the control group(Con,n=10)and the aged T2DM model group(n=30)according to the body weight.The rats in the T2DM model group were fed a high-glucose and high-fat diet,and treated with D-galactose intraperitoneally every day.Meanwhile,rats in the Con group were fed a normal diet,and treated with the equal volume of saline by intraperitoneal injection.After 4 weeks,the T2DM model rats were injected with STZ 25 mg/kg.The Con rats were injected with the same volume of citric acid buffer.Then,fasting blood glucose(FBG)was measured on the14th day.Successful T2DM model was developed when FBG was greater than or equal to 16.7 mmol/L.The T2DM rats were randomly divided into the aged T2DM group(model group),the TP 300 mg/kg group(TP group)and the rosiglitazone 3 mg/kg group(RSG group,n=10,respectively).Then,the rats were given intragastric intervention for 8 weeks.FBG was detected by the blood glucose meter,and the expression of P53 in the kidneys was detected by Western blot.Kidney image and mass were recorded,kidney index was calculated,and 24-hour urinary protein(UP)content was measured using CBB method.The microstructure of renal podocytes was observed by transmission electron microscope(TEM).Finally,the expressions of Nephrin,LC3,P62,HSP60,mTOR,p-mTOR,and PINK1 in kidney were detected by Western blot.Results Compared with the Con group,the level of FBG and the expression of P53 in the model group were increased(P<0.05).The kidney was obviously swollen and enlarged,and both renal index and 24-hour UP content were markedly increased(P<0.05).The basement membrane was extensively thickened,and the podocyte foot process was in fusion and disordered arrangement.The expressions of Nephrin,PINK1 and the ratio of LC3Ⅱ/LC3Ⅰ were reduced.Moreover,the expressions of P62,HSP60,and p-mTOR were increased(P<0.05).Compared with the Model group,the level of FBG and the expression of P53 in the TP group were down-regulated(P<0.05).The swelling of the kidney,the structures of the basement membrane and podocyte foot process were improved.Meanwhile,a large number of autophagosomes or autophagolysosomes were observed.Both renal index and 24-hour UP content were reduced(P<0.05).The expressions of Nephrin,PINK1 and the ratio of LC3Ⅱ/LC3Ⅰ were up-regulated,while the expressions of P62,HSP60,and p-mTOR were down-regulated(P<0.05).Compared with the Model group,no significant difference was observed in the ratio of LC3Ⅱ/LC3Ⅰ and the expression of PINK1 in the RSG group(P>0.05).Conclusion TP can improve renal podocyte damage in the aged T2DM rats,and its mechanism is related to increased mitophagy mediated by the mTOR/PINK1 signaling pathway.
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