Zhongguo quanke yixue (Jul 2024)
Antagonistic Effect of Salidroside on Podocyte Pyroptosis in Diabetic Kidney Disease Rats under Hypoxia Based on NLRP3/IL-1β/TGF-β1 Pathway
Abstract
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.
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