Objective: To observe the therapeutic effect of total triterpenoids of psidium guajava leaves (TTPGL) on diabetic nephropathy (DN) rats, and to explore its regulatory effect on mammalian target of rapamycin (mTOR)/ S6 kinase 1 (S6K1) pathway. Methods: 50 SD rats were established diabetic nephropathy (DN) models by subcutaneous injection of deoxycorticosterone acetate salt combined with high-fat diet. After successful modeling, the rats were randomly divided into Valsartan group; TTPGL low, medium and high dose groups and modelgroup. and 8 SD rats were taken as normal control group. Valsartan group was given valsartan 10 mg·kg-1dissolved in 1 ml·100 g-1 body weight normal saline by gavage, and TTPGL low, medium and high dose groups were given TTPGL 30, 60 and 120 mg·kg-1 dissolved in 1 ml·100 g-1 body weight normal saline by gavage, while the model group and the normal control group were given the same amount of normal saline, once a day for 8 weeks. Fasting blood glucose (FBG), 24-hour urine protein, blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by blood glucose meter, radioimmunoassay and enzyme-linked immunosorbent assay. The pathological changes of kidney were observed by hematoxylin eosin (HE) staining, and the changes of subcellular morphology were observed by transmission electron microscope. The mRNA expressions of mTOR, S6K1, Beclin1, LC3, Nephrin were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of mTOR, S6K1, Beclin1, LC3Ⅱ/Ⅰ, Nephrin and phosphorylated mTOR/mTOR (p-mTOR/mTOR) and phosphorylated S6K1/S6K1 (p-S6K1/S6K1) were detected by Western blot (WB). Results: The success rate of DN modeling was 92.00%. After intervention, FBG, 24 h urine protein, BUN, SCR, mTOR, S6K1 mRNA and protein expressions in renal tissues, p-mTOR/mTOR, p-S6K1/S6K1 levels in renal tissues of model group were higher than those of the normal control group (P<0.05), of which the Valsartan group and TTPGL 3-dose groups were lower than those of the model group (P<0.05). After intervention, the relative expressions of Beclin1, LC3 II/I, Nephrin mRNA and proteins in the model group were lower than those in the normal control group (P<0.05), of which the Valsartan group and TTPGL 3 dose group were higher than those in the model group (P<0.05). The effect of TTPGL was dose-dependent, and there were no significant differences in the above indexes between Valsartan group and TTPGL medium dose group (P>0.05). In the normal control group, the morphology of glomerulus and renal tubules was normal, the structure was clear, and the subcellular structure was normal. In the model group, the basement membrane of glomerulus was significantly thickened, the contour of capsule cavity was seriously irregular and significantly increased, the distribution of cells was seriously uneven and fatty degeneration was common. The renal tubules were severely atrophied and collapsed, and the wall cells were severely irregular, and the subcellular structure was significantly changed. The improvement was observed in Valsartan group and TTPGL 3-dose groups, and the TTPGL high dose group was the closest to the normal control group.Conclusion: TTPGL can reduce the pathological changes of renal tissues, enhance renal function, speculate and inhibit the mTOR/S6K1 pathway, reduce the expressions of mTOR and S6K1 and the levels of p-mTOR/mTOR and p-S6K1/S6K1, and upregulate the expressions of Beclin1, LC3 and Nephrin.
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