Treatise
LIANG Shuang, SONG Chundong, DUAN Fengyang, ZHANG Bo, ZHANG Xia, DING Ying, REN Xianqing, ZHAI Wensheng
Objective:To investigate the effect of multi-glycosides of Tripterygium wilfordii (GTW) on VDR/DDIT4/mTOR signaling pathway in diabetic kidney disease (DKD) rats.Methods:Thirty rats were randomly divided into normal group (n=6) and model group (n=24). The normal group was fed with normal diet, and the model group was established with high-fat and high-sugar feed and one-time intraperitoneal injection of streptozotocin (STZ). After the model was successfully established, the rats were randomly divided into model group, Daiwen group and GTW group, and gastric lavage was started from the 9th week. The rats in Daiwen group were gavaged with valsartan and GTW group were gavaged with GTW. After 6 weeks’ continuous gavage, serum albumin (ALB), alanine aminotransferase (ALT), urea nitrogen (BUN), creatinine (SCr), glucose (GLU), cholesterol (CHO), triglyceride (TG) and total 24 hour total urine protein (24 h-UTP) were detected. The expression levels of VDR, DDIT4, mTOR, phosphorylated mTOR (p-mTOR), autophagy gene unc-51-like kinase 1 (ULK1) mRNA and protein were detected by PCR and Western Blot, respectively.Results: Compared with the normal group, 24 h-UTP, BUN, SCr, ALT, CHO, TG and GLU in the model group were significantly increased (P<0.01), while ALB was significantly decreased (P<0.01), the expression of VDR, DDIT4, ULK1 protein and mRNA in renal tissue decreased significantly (P<0.01), while the expression of mTOR protein and mRNA increased significantly (P<0.01), and the expression of p-mTOR protein increased significantly (P<0.01), pathology of renal tissue was obviously damaged. Compared with the model group, 24 h-UTP, BUN, SCr, ALT, CHO, TG and GLU in Daiwen group and GTW group decreased significantly (P<0.01), while ALB increased significantly (P<0.01), the expression of VDR, DDIT4, ULK1 protein and mRNA in renal tissue increased significantly (P<0.01), while the expression of mTOR protein and mRNA decreased significantly (P<0.01), and the expression of p-mTOR protein decreased significantly (P<0.01), glomerular morphology was basically normal, mesangial cell proliferation and inflammatory cell infiltration were reduced.Conclusion: GTW can reduce 24 h-UTP, protect renal function, reduce blood lipid and improve renal pathological injury in DKD rats, and its mechanism may be related to its regulation of VDR/DDIT4/mTOR signaling pathway expression and improvement of autophagy.