The Molecular Mechanism Of Shen Shuai Kang Enemas Treating Acute Kidney Injury Based On Network Pharmacology And CHOP-ERO1α Pathway

OBJECTIVE: Acute kidney injury is a common acute and critical disease with high mortality.Shen Shui Kang enemas is currently the only Chinese patent medicine on the market with acute kidney injury as indication,which has definite clinical effect.The purpose of this study is to clarify the mechanism of Shen Shui Kang enemas in the treatment of acute kidney injury and to improve the clinical therapeutic effect of acute kidney injury.METHODS: 1.The network pharmacology method is adopted,and the pharmacology and bioinformatics databases of traditional Chinese medicine(TCMSP,OMIM,TTD,GAD,Pharm Gkb,Uniprot,Di GSe E,DAVID,Omicshare and other databases)are used to explore the target sites for the effect of Shen Shui Kang enemas on acute kidney injury and the related targets for acute kidney injury.Through the enrichment analysis of the core targets,the mechanism of Shen Shui Kang enemas in the treatment of acute kidney injury is predicted.2.According to the predicted results of the network,the molecular mechanism of Shen Shuai Kang enemas for the treatment of acute renal injury is determined by molecular biological methods(CFSE/PI staining,rt-pcr,Western blot).RESULTS:1.Prediction based on network pharmacological method: Shen Shuai Kang enemas is mainly used to treat acute kidney injury by regulating apoptosis.The mechanism of regulating apoptosis is closely related to endoplasmic reticulum stress.Compared with the control group,the expressions of GRP78,Bax and caspase-3 in the hypoxia reoxygenation model group are increased,and hypoxia reoxygenation can lead to the apoptosis of renal tubular epithelial cells(HK-2)and endoplasmic reticulum stress.Compared with the model group,GRP78,Bax and caspase-3 expressions are decreased in the Shen Shuai Kang group,indicating that Shen Shuai Kang enemas could inhibit HK-2 cell apoptosis and endoplasmic reticulum stress.Compared with the control group,hypoxic reoxygenation can activate downstream pathways of the endoplasmic reticulum and up-regulate the expressions of CHOP and ERO1-α.Compared with the model group,the expression of CHOP and ERO1-α was down-regulated by shenshuaikang enema.It is suggested that the mechanism of Shen Shuai Kang enemas inhibiting HK-2 cell apoptosis is closely related to CHOP-ERO1α pathway.CONCLUSION: The network pharmacology and molecular biology methods show that Shen Shuai Kang enemas can effectively treat acute renal injury,and its main mechanism is related to the regulation of endoplasmic reticulum stress and apoptosis.Shen Shuai Kang inhibits renal tubular epithelial cell apoptosis by regulating CHOPERO1α pathway,which is the molecular mechanism of treating acute renal injury.