Effects Of Manshenkangning On Pathway Of PERK-ATF4in Endoplasmic Reticulum Stress In Renal Interstitial Fibrosis Rats

OBJECTIVE: To investigate the effect and mechanism of Manshenkangning onendoplasmic reticulum stress PERK-ATF4pathway in renal interstitial fibrosis rats.METHODS:60male Wistar rats were randomly selected from only the normal group,and the remaining rats with adenine orally renal interstitial fibrosis （RIF） model.21days after modeling success, randomized, the rats were divided into model group,losartan group (10mg· kg^-1· d^-1), the Manshenkangning (7.5g·kg^-1·d^-1),(15g· kg^-1· d^-1), high (30g·kg^-1·d^-1) group, each group was given losartan,Manshenkangning and distilled water, administered continuously for30days. The endof the experiment, specimens of blood, urine, and kidney tissue samples, detection Scr,BUN,24hMTP estimate eGFR, HE and Masson staining pathological changes ofrenal tissue, the immunohistochemical detection GRP78, TUNEL assay renal tissue ofrenal tubular epithelial cells withered death, GRP78, ATF4, CHOP mRNA expressionlevel was measured by real-time quantitative PCR.RESULTS: SCR, BUN,24hMTP of Losartan group and Manshenkangning high-dosegroup were significantly decreased than the other group（P <0.01）,the eGFR rise （P<0.01）. Compared with model group, the treatment groups RIF lessened.GRP78expression levels and tubular epithelial cell apoptosis levels of Losartan group andManshenkangning high-dose group were decreased （P <0.05）. GRP78, ATF-4, CHOPmRNA expression levels of Losartan group and Manshenkangning high-dosecompared with model group （P <0.05） lower.CONCLUSION: ERS participate in the development of renal interstitial fibrosis.Manshenkangning can reduce the apoptosis of renal tubular epithelial cells, theoverexpression of PERK-eIF2-ATF4-CHOP pathway can good inhibition with kidneyprotection, which may be an important mechanism world.