益肾化湿颗粒通过miR-339-5p靶向调控TGF-β1/Smad通路对慢性肾小球肾炎模型大鼠的肾脏保护作用及其机制研究

OBJECTIVE To investigate the renal protective effect and mechanism of Yishen Huashi granules in chronic glomerulonephritis model rats by targeting and regulating transforming growth factor-β1(TGF-β1)/Smad pathway through miR-339-5p. METHODS SD rats were divided into sham operation group,model group,Yishen Huashi granules group,benazepril group,Yishen Huashi granules+antagomir negative control (NC) group,Yishen Huashi granules+miR-339-5p antagomir group,and Yishen Huashi granules+SRI-011381 group.The levels of 24 h urinary protein,serum creatinine (Scr) and blood urea nitrogen (BUN) of rats were measured by an automatic biochemical analyzer;the levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and interleukin-6(IL-6) were detected by ELISA;the expression of miR-339-5p in renal tissue was detected by qRT-PCR;the expression of nuclear factor E2 related factor 2(NRF2) and heme oxygenase 1(HO-1) in rat kidney was detected by immunohistochemistry;HE and Masson staining were used to detect the pathological changes and the degree of fibrosis of rat kidney;Western blot was used to detect the expression of TGF-β1 p-Smad2/3 and Smad7 proteins in renal tissue;the relationship between miR-339-5p and TGF-β1 was verified. RESULTS Compared with the sham operation group,the model group had abnormal renal function,increased oxidative stress,severe renal tissue pathological damage and fibrosis,inflammatory factors,TGF-β1 and p-Smad2/3 protein expression increased,the expression of miR-339-5p and Smad7 proteins decreased (P<0.05);compared with that in the model group,the change trend of corresponding indexes in Yishen Huashi granules group and benazepril group was opposite to the above (P<0.05);miR-339-5p antagomir or SRI-011381 attenuated the renal protective effect of Yishen Huashi granules in chronic glomerulonephritis model rats.MiR-339-5p targeted and regulated the expression of TGF-β1. CONCLUSION Yishen Huashi granules may protect kidney of model rats with chronic glomerulonephritis by up-regulating miR-339-5p and targeted inhibiting TGF-β1/Smad pathway.