Effects Of Yishen Capsule On PERK/CHOP Signaling Pathway In Diabetic Nephropathy Rats

Objective:To investigate the protective effect of Yishen capsule on diabetic nephropathy rats and the effect of ER stress on PERK/CHOP pathway in renal tissues.Methods:Forty healthy male SD rats were randomly divided into 10 normal control groups(N group)and the other 30 rats were intraperitoneally injected with streptozotocin(STZ)55mg/kg for 3 consecutive days to establish diabetic nephropathy model.The experimental group was divided into diabetic nephropathy group(DN group),Yishen Capsule group(YS group)and resveratrol group(Re group),with 10 rats in each group.Each rat in YS group was given yishen Capsule 625mg/kg/d,each rat in Re group was given resveratrol 20mg/kg/d,and the N and DN groups were given the same amount of normal saline daily for 8 weeks.At the end of 0W,4W and 8W,blood glucose,urinary protein quantification at 24 h and urinary microalbumin were measured.BUN,Scr,TG,TC and other biochemical indexes were measured at the end of 8W.Histopathological changes were observed by HE staining,PAS staining and Masson staining.Immunohistochemical technique was used to detect the expression of PERK and CHOP in renal tissues of rats.Results:(1)General conditions: The rats in group N had normal blood glucose,smooth and shiny hair,normal water intake,mental state and sensitive reaction;Compared with N group,blood glucose in DN group was significantly increased,hair dark and dull accompanied by hair loss,listlessness,drinking water and food intake were significantly increased,and urine volume was increased;Compared with DN group,the blood glucose level of YS group and Re group was decreased,and the spirit,activity and water intake were generally improved.(2)Blood and urine indicators: Compared with N group,BUN,Scr,TG,TC,urinary microalbumin concentration and 24 h urinary protein quantitative level in DN group were increased(P < 0.05);Compared with DN group,BUN,Scr,TG,TC,urinary microalbumin concentration and 24 h urinary protein quantitative level of YS group and Re group were decreased(P < 0.05).(3)Pathological changes of renal tissue: Compared with the N group,HE staining in the DN group showed glomerular hypertrophy,reduced volume of renal tubular epithelial cells,obvious narrowing and deformation of lumen,and vacuolar degeneration.PAS staining showed significant increase of red glycogen deposits in the glomerular,and Masson staining showed massive deposition of collagen fiber tissue in the interstitium.Compared with DN group,YS group,Re group,renal tissue pathological damage was reduced.(4)The expression of PERK and CHOP: Immunohistochemical results showed that compared with N group,the expression of PERK and CHOP was increased in DN group(P < 0.05).Compared with DN group,YS group and Re group had lower expression of PERK and CHOP(P < 0.05).Conclusion:Yishen capsule may play a protective role in diabetic nephropathy by regulating the PERK/CHOP signaling pathway and improving endoplasmic reticulum stress.