Background Salidroside has been shown to protect diabetic kidney disease(DKD)rats,however,whether it is equally effective in a hypoxic environment and the specific mechanism of action remain unclear.Objective To observe the effects of salidroside on biochemical parameters,renal tissue pathological lesion,and the expression of cell pyroptosis-related proteins in a rat model of DKD under hypoxia,and explore its mechanisms of action.Methods From March 2022 to March 2023,forty 6-week-old SPF-grade SD male rats were used,with eight randomly selected as the control group,the remaining were modeled.Twenty-four DKD model rats were randomly divided into three groups of the model group,salidroside group,and salidroside+nod-like receptor protein 3(NLRP3)activator group for intervention,with 8 in each group.After the intervention,blood was collected from the abdominal aorta for biochemical parameter testing,hematoxylin-eosin(HE)staining,and transmission electron microscopy were used to observe renal pathological changes.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of interleukin(IL)1β and IL-18.Western blotting was used to measure the expression levels of Caspase-1,Gasdermin D(GSDMD),NLRP3,and transforming growth factor β1(TGF-β1)in renal tissue.Results The body weight of the rats after modeling was significantly lower than that of the control group(P<0.05).Compared to the control group,the levels of triglyceride(TG),total cholesterol(TC),fasting blood glucose(FBG),urinary microalbumin(UMA),blood urea nitrogen(BUN),and serum creatinine(Scr)were significantly higher in the model group(P<0.05).Compared to the model group,the BUN,UMA,and Scr levels were significantly lower in the salidroside group(P<0.05).Compared to the salidroside group,the UMA,BUN,and Scr levels were significantly higher in the salidroside+NLRP3 activator group(P<0.05).HE staining and transmission electron microscopy revealed that renal tissue pathological changes in the salidroside group were significantly reduced than the model group,and aggravated in the salidroside+NLRP3 activator group.Compared to the control group,serum IL-1β and IL-18 levels were significantly higher in the model group(P<0.05);these levels were significantly lower in the salidroside group compared to the model group(P<0.05),and higher in the salidroside+NLRP3 activator group compared to the salidroside group(P<0.05).Compared to the control group,the expression of Caspase-1,GSDMD,NLRP3,and TGF-β1 proteins was significantly higher in the model group(P<0.05);it was significantly lower in the salidroside group compared to the model group(P<0.05),and higher in the salidroside+NLRP3 activator group compared to the salidroside group(P<0.05).Conclusion Salidroside exerted therapeutic effects on DKD rats in a hypoxic environment without reducing blood glucose and lipid levels,this effect may be related to the inhibition of NLRP3,affecting the NLRP3/IL-1β/TGF-β1 signaling pathway,ultimately improving podocyte pyroptosis injury.
万方数据
维普
