参芪地黄汤通过抑制氧化应激和抗凋亡改善糖尿病肾病的机制研究OA

Objective:To investigate the protective effect and mechanism of Shenqi Dihuang Decoction on renal injury in mice with diabetic kidney disease(DKD).Methods:Twenty-four 10-week-old db/db mice were randomly divided into the DKD model group,low-dose Shenqi Dihuang Decoction(SQDHD)group and high-dose SQDHD group,with 8 mice in each group.Another 8 10-week-old db/m mice were assigned as the healthy control group.The high and low-dose SQDHD groups were given intragastric administration of SQDHD at the corresponding doses,while the healthy control group and DKD model group received an equal volume of distilled water via intragastric administration,once daily for 8 consecutive weeks.Blood and urine samples were collected to detect the levels of fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),serum creatinine(SCr)and microalbumin(mALB).Hematoxylin-eosin(HE)staining,Masson staining and periodic acid-Schiff(PAS)staining were performed to observe the pathological morphological changes of the kidney.TUNEL staining was used to detect the apoptosis of renal tissue cells.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in renal tissues were determined by WST-1 assay,microplate assay and thiobarbituric acid assay,respectively.Western blot was adopted to detect the protein expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in renal tissues of mice.Results:Compared with the healthy control group,in the DKD model group the levels of FBG,TC,TG,BUN,SCr and mALB were significantly increased(P<0.05),the protein expressions of Nrf2 and HO-1 were significantly decreased(P<0.05),the activities of SOD and GSH-Px were reduced(P<0.05),the content of MDA was elevated(P<0.05),and the apoptosis of renal tissue cells was significantly increased(P<0.05).HE,Masson and PAS staining showed that the mice in the DKD model group presented glomerular hypertrophy,basement membrane thickening,interstitial inflammatory cell infiltration and obvious interstitial fibrosis.Compared with the DKD model group,SQDHD intervention alleviated glomerular hypertrophy,with a small amount of interstitial inflammatory cell infiltration and no obvious collagen fiber deposition;FBG,TC,TG,BUN,SCr and mALB were decreased(P<0.05),SOD and GSH-Px were enhanced(P<0.05),MDA was reduced(P<0.05),and Nrf2 and HO-1 expressions were increased(P<0.05),and the apoptosis of renal tissue cells was significantly reduced after SQDHD intervention(P<0.05).Conclusion:SQDHD exerts antioxidant and anti-apoptotic effects on DKD mice,alleviates renal pathological damage and exerts a renoprotective effect by inhibiting cellular oxidative stress to attenuate apoptosis in renal tissues.