Objective To observe the effect and mechanism of Manshen Kangning Formula（formula for chronic kidney disease

MKF）on endoplasmic reticulum stress in renal tissue of renal interstitial fibrosis rats.Methods Sixty male Wistar rats were selected

seven wererandomly set into normal group

and other 53were given 2.5%adenine to make renal interstitial fibrosis model.After modeling

fifty successful model rats were randomized into model group

losartan group

MKF small-dose group

MKF middle-dose group and MKF large-dose group

with 10in each.The treatment groups were given losartan suspension[10mg/（kg·d）]

small-dose MKF suspension[7.5g/（kg·d）]

middle-dose MKF suspension[15g/（kg·d）]and large-dose MKF suspension[30g/（kg·d）]respectively and the same amount of distilled water was given to the normal group and model group intragastrically.The administration lasted for 30days.The serum creatinine（SCr）

blood urea nitrogen（BUN）

24-hour urinary protein（24hUP）and estimated glomerular filtration rate（eGFR）were detected.The renal histopathological changes were observed with HE and Masson staining.The glucose-regulated protein 78（GRP78）was detected with immunohistochemical staining and the apoptotic cells were detected with TUNEL staining.Real Time PCR was used to detect the expression levels of GRP78mRNA

activating tranSCription factor 4（ATF4）mRNA and CCAAT/enhancer-binding protein homologous protein（CHOP）mRNA.Results Comparing with the model group

the levels of SCr

BUN and 24hUP were significantly decreased（P<0.01）

but the eGFRs were significantly increased in the losartan group and MKF groups（P <0.01）.Apoptosis

necrosis and shedding in renal tubular epithelial cells

tubular dilatation

inflammatory cell infiltration

adenine metabolite deposition and collagen fibers in renal interstitial tissue could be seen under the microscope in the model group.Comparing with the model group

the pathological changes were lighter in the losartan group and MKF groups.Comparing with the model group

GRP78expressions and apoptosis levels were significantly decreased in the losartan group and MKF large-dose group（P<0.05）.Comparing with the model group

the expressions of GRP78mRNA

ATF-4mRNA and CHOP mRNA were significantly decreased（P<0.05）.Conlcusion Endoplasmic reticulum stress is related to the occurrence and development of renal interstitial fibrosis.MKF can attenuate renal interstitial fibrosis and protect kidney function

which may be relevant to regulating the over expression of PERK-eIF2α-ATF4-CHOP pathway.