Based On PERK-eIF2α-ATF4-CHOP Signaling Pathway To Explore The Mechanism Of Shenshuai Nutrition Capsule On Improving Renal Endoplasmic Reticulum Stress In CRF Rats

Background:Chronic renal failure is the outcome of the continuous progression of chronic kidney disease.It has a poor prognosis and requires huge medical expenses.It brings a heavy economic burden to society and families.Studies in recent years have shown that endoplasmic reticulum stress may be a key link in the pathogenesis and progression of kidney disease,and regulation of ERS may play an important role in renal protection.Traditional Chinese medicine compound Shenshuai nutrition capsule is an agreement prescription for chronic renal failure malnutrition,which was summarized by Professor Wei Lianbo based on the theory of Chinese medicine and years of clinical experience.Clinical observations and pharmacodynamic studies have confirmed that Shenshuai Nutrition Capsules can significantly improve the renal function and malnutrition status of CRF patients,but its mechanism of action is unknown.Objective:To explore the protective effect and mechanism of Shenshuai Nutrition Capsule on renal injury in rats with chronic renal failure.Methods:The model of CRF rats were made by 5/6 nephrectomy,and the sham operation group,model group,Shenshuai nutrition capsule group and KA group were established.Shenshuai nutrition capsule group and KA group were given corresponding drugs for 8 weeks.The body weight in each group was measured at 0,4 and 8 weeks after treatment.The levels of Scr,BUN and ALB in each group were measured before treatment and after treatment.H&E staining,Masson staining and TGF-β immunohistochemical staining were used to evaluate the effect of Shenshuai nutrition capsule on renal histological morphology of CRF rats.The activity of superoxide dismutase(SOD),catalase(CAT)and the level of malondialdehyde(MDA)were used as the standard to detect the effect of Shenshuai nutrition capsule on the level of oxidative stress in CRF rats.Hoechst 33342 staining was used to detect the effect of Shenshuai nutrition capsule on renal cell apoptosis in CRF rats.Western blot was used to detect the expression of cleaved Caspase-3,cleaved Caspase-12,Bax,Bcl-2,p-PERK,p-eIF2a,ATF4 and CHOP.qPCR wsa used to detect the expression of Bax,Bcl-2,ATF4 and CHOP.Results:The results in vivo showed that Shenshuai nutrition capsule could significantly increase the body weight,reduce the levels of SCR and BUN,increase the level of ALB,reduce the expression of TGF-β,improve renal function and renal fibrosis of CRF rats.At the same time,Shenshuai nutrition capsule can significantly improve the activities of antioxidant enzymes SOD and CAT,reduce the level of oxidative metabolite MDA,alleviate OS reaction and inhibit renal cell apoptosis in the kidney under CRF condition.Based on the mechanism of Shenshuai nutrition capsule,WB results showed that:after the intervention of Shenshuai nutrition capsule,the protein levels of cleaved Caspase-3,cleaved Caspase-12,Bax,p-PERK,p-eIF2α,ATF4 and CHOP in renal tissue of CRF rats decreased significantly,while the protein levels of Bcl-2 in renal tissue of CRF rats increased significantly.qPCR results showed that:after the intervention of Shenshuai nutrition capsule,the mRNA levels of Bax,ATF4 and CHOP in renal tissue of CRF rats decreased significantly,while the mRNA levels of Bcl-2 in renal tissue of CRF rats increased significantly.Conclusion:Shenshuai nutrition capsule can improve the renal injury of CRF rats,and its mechanism may be to reduce the oxidative stress response,and then regulate the expression levels of endoplasmic reticulum stress related molecules p-PERK,p-eIF2α,ATF4 and CHOP to regulate the expression of cell apoptosis related molecules cleaved Caspase-3,cleaved Caspase-12,Bax and Bcl-2.Therefore,it can inhibit the apoptosis of renal cells and protect the kidney of CRF rats.