益肾排毒方调控ROS/TXNIP/NLRP3通路对慢性肾衰竭大鼠肾纤维化的影响OA
Effects of Yishen paidu formula on renal fibrosis in rats with chronic renal failure by regulating the ROS/TXNIP/NLRP3 pathway
目的 通过活性氧(ROS)/硫氧还蛋白相互作用蛋白(TXNIP)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)通路,探讨益肾排毒方对慢性肾衰竭(CRF)大鼠肾纤维化的作用及机制.方法 将大鼠随机分为对照组、模型组、益肾排毒方低剂量(益肾排毒方-L)组、益肾排毒方高剂量(益肾排毒方-H)组、益肾排毒方-H+携带阴性对照序列的pcDNA载体(pcDNA-NC)组、益肾排毒方-H+携带TXNIP基因的pcDNA载体(pcDNA-TXNIP)组,每组10只.除对照组外,其余大鼠均通过喂养含0.5%腺嘌呤的饲料构建CRF模型,并灌胃或尾静脉注射相应药物或生理盐水,每日1次,连续8周.末次给药后,检测各组大鼠血肌酐(Scr)、尿素氮(BUN)、活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β水平;观察肾组织病理变化;检测肾组织中胶原蛋白Ⅲ(Collagen Ⅲ)、α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、TXNIP、NLRP3蛋白表达情况.结果 与模型组比较,益肾排毒方-L组和益肾排毒方-H组大鼠肾组织病理损伤和纤维化均明显缓解,Scr、BUN、ROS、MDA、TNF-α、IL-6、IL-1β水平和Collagen Ⅲ、α-SMA、TGF-β1、TXNIP、NLRP3蛋白表达水平均明显/显著降低,SOD水平均显著升高(P＜0.05),且益肾排毒方-H组变化更显著(P＜0.05);与益肾排毒方-H+pcDNA-NC组比较,益肾排毒方-H+pcDNA-TXNIP组大鼠上述指标水平均显著逆转(P＜0.05).结论 益肾排毒方可通过抑制ROS/TXNIP/NLRP3通路延缓CRF大鼠肾纤维化.
OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure(CRF)through the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.METHODS Rats were randomly divided into control group,model group,Yishen paidu formula low-dose(Yishen paidu formula-L)group,Yishen paidu formula high-dose(Yishen paidu formula-H)group,Yishen paidu formula-H+pcDNA-NC group,and Yishen paidu formula-H+pcDNA-TXNIP group,with 10 rats in each group.Except for control group,all other rats were fed a diet containing 0.5%adenine to establish a CRF model;the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein,once daily,for 8 consecutive weeks.After the last administration,the levels of serum creatinine(Scr),blood urea nitrogen(BUN),ROS,superoxide dismutase(SOD),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β were measured in each group.Pathological changes in renal tissue were observed,and the protein expression levels of Collagen Ⅲ,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),TXNIP and NLRP3 in renal tissue were detected.RESULTS Compared with model group,the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated.The levels of Scr,BUN,ROS,MDA,TNF-α,IL-6 and IL-1β,and the protein expressions of Collagen Ⅲ,α-SMA,TGF-β1,TXNIP and NLRP3 were significantly decreased,while SOD levels were significantly increased(P＜0.05).Moreover,the changes were more pronounced in the Yishen paidu formula-H group(P＜0.05).Compared with Yishen paidu formula-H+pcDNA-NC group,above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly(P＜0.05).CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.
冯立;彭博文;彭斌;冯雪;朱双益;熊玮;胡溪;孙小慧
武汉市中医医院肾病科,武汉 430014武汉市中医医院骨科,武汉 430014武汉市中医医院肾病科,武汉 430014武汉市中医医院肾病科,武汉 430014武汉市中医医院肾病科,武汉 430014武汉市中医医院肾病科,武汉 430014武汉市中医医院肾病科,武汉 430014武汉市中医医院肾病科,武汉 430014
医药卫生
益肾排毒方慢性肾衰竭肾纤维化ROS/TXNIP/NLRP3通路
Yishen paidu formulachronic renal failurerenal fibrosisROS/TXNIP/NLRP3 pathway
《中国药房》 2026 (2)
174-179,6
武汉市知识创新专项(No.2023020201020556)武汉市中医药科研项目(No.WZ22Q51)
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