Effect of Catalpol on the Expression of PERK and CHOP in Renal Endoplasmic Reticulum Pathway with Diabetic Nephropathy Rats

GUO Xue; LIU Ping; LIANG Zhihui; WANG Nan; LI Zongze; WANG Xinghang; TIAN Juan

Abstract：Objective To investigate the effects of catalpol on the renal tissue structure and the expression of PERK and CHOP in diabetic nephropathy(DN)rats,and to explore the regulatory effect of catalpol on the renal endoplasmic reticulum stress pathway and its protective effect on renal injury.Methods After feeding 60 SD rats for 1 week,they were randomly divided into control group,model group,low-dose catalpol protection group,medium-dose catalpol protection group and high-dose catalpol protection group,with 12 rats in each group.The rat DN model was established by intraperitoneal injection of STZ.After 6 weeks of inadministration of catalpol,samples were prepared by routine sampling.HE and PAS staining were used for histological examination of kidney.Immunohistochemistry and Western Blot were used to observe the distribution and protein expression of PERK and CHOP in renal tissues.Results The results of HE and PAS staining showed that the kidney tissue of the control group was normal;in model group,there were glomerular deformation,basement membrane thickening,mesangial hyperplasia,renal tubule degeneration,epithelial cell vacuolation and interstitial edema;PAS positive was obvious.After the intervention of catalpol,the pathological changes of renal tissue were improved and PAS positive was weakened,especially in the protection group of medium and high dose catalpol,mesangial proliferation was reduced,basement membrane was thickening and renal tubule lesions were significantly reduced.Immunohistochemical results showed that PERK and CHOP were localized in the cytoplasm of proximal and distal tubule epithelial cells;compared with the control group,the expressions of PERK and CHOP in kidney tissue of model group were significantly increased(P＜0.001);compared with model group,PERK and CHOP expression decreased in kidney tissue of catalpol protected group,especially in medium and high dose catalpol protected group(P＜0.01,P＜0.001).Western Blot results showed that compared with the control group,the expressions of PERK and CHOP protein in kidney tissue of model group were significantly increased(P＜0.001);compared with model group,PERK protein expression in catalpol protected group was decreased in a dose-dependent manner(P＜0.05,P＜0.001).There was no significant change in CHOP expression in low-dose catalpol protection groups;CHOP expression was decreased in medium-dose and high-dose catalpol protection groups(P＜0.01,P＜0.001).Conclusion Catalpol may down-regulate the expression of PERK and CHOP in renal tissue,maintain endoplasmic reticulum homeostasis,and alleviate renal injury in diabetic nephropathy.