ABSTRACT
Objective To investigate the specific expression of endoplasmic reticulum stress-related GRP78 and CHOP in podocyte of MKR mice with diabetic nephropathy (DN);To discuss the intervention effect of Zuogui Jiangtang Yishen Decoction (ZGJTYS). Methods 8-week old MKR mice were randomly divided into five groups:blank group, model group, ZGJTYS group, 4-Phenylbutyric acid group, gliquidone+benazepril group, and normal control group consisting of wild type C57BC/6 mice, 10 mice per group. All mice from model group and each treatment group received high-fat diet feed and unilateral nephrectomy to make the DN model. Mice from treatment groups received medicine intervention for four weeks. The levels of FBG were detected by electrochemical detection method, and the UmAlb was detected by ELISA. The expressions of GRP78, CHOP mRNA, and protein were detected by RT-PCR and Western blot. The morphological structure changes of the podocytes were observed by transmission electron microscopes. Results Compared with blank group, FBG and UmAlb in the model group increased significantly (P<0.01);the expressions of GRP78 mRNA and protein markedly decreased (P<0.01);the expressions of CHOP mRNA and protein increased (P<0.01). Compared with the model group, FBG and UmAlb in each treatment group significantly decreased (P<0.01);the expressions of GRP78 mRNA and protein in the ZGJTYS group and 4-Phenylbutyric acid group increased (P<0.01), the expressions of CHOP mRNA and protein decreased (P<0.01). The renal pathological lesions of each treatment group were significantly improved compared with model group. Conclusion ZGJTYS Decoction can effectively improve the damaged podocyte induced by endoplasmic reticulum stress, delay DN progress.
ABSTRACT
Objective To investigate the effects of Zuogui Jiangtang Yishen decoction (ZGJTYS) on the expression of nephrin and podocin in podocyte of MKR mice with diabetic nephropathy (DN), and explore its mechanism. Methods Forty MKR mice (8 weeks old) were randomly divided into four groups as follows:negative control group (group A), DN model group (group B), ZGJTYS group (group C) and positive control group (group D, Gliquidone and benazepri). All mice from group B, C and D were received high-fat diet feed and unilateral nephrectomy. Four weeks after operation, all mice were received drug intervention, and four weeks later, all mice were put to death. The levels of UmAlb were observed by ELISA, the serum BUN and Cr by biochemical, and the FBG by electrochemical detection method. The nephrin and podocin mRNA expression were measured by RT-PCR and the protein expression by western blotting. The morphological structure changes of the podocytes were observed by transmission electron microscopes. Results As compared with group A, FBG, BUN, SCr and urine UmAlb in the mice of group B increased significantly (P<0.01), the expression level of nephrin and podocin mRNA and protein were markedly decreased (P<0.01). After intervention of drugs, all biochemical indicators above in the mice of group C and D significantly decreased (P<0.01), the expression level of nephrin and podocin mRNA and protein were markedly increased (P<0.01, P<0.05), compared with group B. The renal pathological lesions of group C and D were significantly improved compared with group B. Conclusion ZGJTYS decoction exerts reno-protective effect via reinstating nephrin and podocin expression to repair the damaged podocyte.