关键词: 糖尿病肾病, 肾安汤, 线粒体稳态, 内质网应激, ATP, 线粒体膜电位

Abstract: Objective To investigate whether Shen’an decoction alleviates renal injury in diabetic kidney disease(DKD)rats by improving mitochondrial homeostasis and endoplasmic reticulum stress. Methods The rat model of DKD was established.Venous blood from the tail of the rats and urine were collected at 0,2,4,and 8 weeks respectively.The fasting blood glucose content and the ratio of urinary microalbumin to urinary creatinine(ACR)were detected.The levels of renal function indicators such as serum creatinine(sCr),blood urea(BUN),and serum uric acid(UA),as well as liver function indicators such as albumin(ALB),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were detected by reagent kits.The pathological changes of rat renal tissues were observed by HE staining,PAS staining,Masson staining,and PASM staining.The ATP content,mitochondrial membrane potential(MMP),mitochondrial functional proteins(mitochondrial-related proteins cytochrome C[Cyt C],mitochondrial transcription factor A[TFAM]),and endoplasmic reticulum stress proteins(CHOP,PERK)in renal tissues were detected by using kits,flow cytometry and Western blot,and the oxidative stress levels(MDA,SOD,GSH)were evaluated. Results Compared with the normal group,the fasting blood glucose and urinary ACR of DKD rats in the model group were significantly increased at 0,2,4,and 8 weeks of drug intervention.Renal pathological staining showed that in the model group,narrowing of the glomerular lumen in the renal tissue,edema of the renal tubular epithelial cells,and infiltration of inflammatory cells could be observed,and there were thickening of the glomerular basement membrane,hyperplasia of collagen fibers and glycogen deposition in the tubular epithelium and interstitium of the kidneys,glomerular sclerosis and interstitial fibrosis.After treatment with Shen’an decoction,the above-mentioned pathological changes were significantly improved.Compared with the normal group,the ATP content and MMP expression in the renal tissues of the model group decreased,while the expression levels of Cyt C and TFAM significantly increased.After treatment with the Shen’an decoction,all the above-mentioned changes were reversed,and the pathological damage of the kidneys was significantly improved,suggesting that Shen’an decoction plays an important role in the mitochondrial ecological balance of DKD rats.In addition,the expression levels of reticulum stress-related proteins(CHOP and PERK)and the content of GSH in the renal tissues of rats in the model group were significantly higher,while the contents of MDA and SOD were significantly lower than those in the normal group.After treatment with Shen’an decoction,all the above-mentioned indicators were reversed.It indicates that Shen’an decoction alleviates renal injury by influencing endoplasmic reticulum stress in cells. Conclusion Shen’an decoction inhibits endoplasmic reticulum stress in rats with DKD and promotes mitochondrial homeostasis to alleviate renal tissue damage in rats with DKD.

Key words: diabetic kidney disease, shen’an decoction, mitochondrial homeostasis, endoplasmic reticulum stress, ATP, mitochondrial membrane potential