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| Effect of Huangqin Decoction on NF-κB/NLRP3/Caspase-1 Signaling Pathway and Pyroptosis in Kidney of Diabetic Nephropathy Rats |
LIU Jia1,YAN Bao-fei1,ZHANG Jing-zheng1,MA Yu-ting1,TIAN Zhao-hui2,ZENG Qing-qi1,**( ) |
1 Jiangsu Health Vocational College, Nanjing 211800, China
2 The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China |
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Abstract To study the effect of Huangqin Decoction on nuclear factor kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1)-dependent pyroptosis pathway in diabetic nephropathy (DN) rat model. Methods: Rats were randomly divided into control group, model group, irbesartan group (27 mg/kg), and Huangqin Decoction low- and high-dose groups (5 g/kg and 20 g/kg), and the DN rat model was induced by high-fat diet for 6 weeks combined with a single intraperitoneal injection of streptozotocin (35 mg/kg). Serum fasting blood glucose (FBG), total cholesterol (TC), triacylglycerol (TG), urine protein (UP), blood urea nitrogen (BUN), serum creatinine (Scr), interleukin 1β (IL-1β) and IL-18 levels were measured after 6 weeks of gavage administration; renal pathological changes were observed by HE and Masson staining; renal NF-κB/NLRP3/Caspase-1/pyroptosis pathway-related proteins and positive cell expression were detected by Western blot and immunohistochemistry. Results: Compared with the control group, the levels of FBG, TC, TG, UP, BUN, Scr, IL-1β and IL-18 were significantly increased in the model group (P<0.01); the kidneys showed pathological changes such as increased glomerular volume and basement membrane thickening, tubular lumen expansion, inflammatory infiltration and fibrosis; the phosphorylation levels of NF-κB in kidney tissues and NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, IL-1β and gasdermin D (GSDMD) protein expression were significantly increasedc (P<0.01); NLRP3 and GSDMD positive cells expression in renal tissue were significantly increased P<0.01). Compared with the model group, the above-mentioned blood glucose, lipids, renal function and inflammatory factor levels were significantly improved in the Huangqin Decoction groups (P<0.05, P<0.01); renal glomerular and tubular structures were normalized, and the degree of inflammatory infiltration and fibrosis was improved; the phosphorylation levels of NF-κB in renal tissue as well as NLRP3, ASC, Caspase-1, IL-1β and GSDMD protein expressions were significantly reduced (P<0.05, P<0.01); renal tissue NLRP3 and GSDMD positive cells expression were significantly reduced (P<0.05, P<0.01). Conclusion: Huangqin Decoction exerts a definite effect on DN rats, at least partly, through inhibition of the NF-κB/NLRP3/Caspase-1-dependent pyroptosis signaling pathway.
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Received: 13 September 2022
Published: 07 December 2022
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