清肾颗粒对腺嘌呤诱导肾纤维化大鼠的铁死亡及寡聚化结构域样受体蛋白3炎症小体活性的影响  

Effect of Qingshen Granules on Ferroptosis and NLRP3 Inflammasome Activity in Rats with Adenine-Induced Renal Fibrosis

作　　者：韦庆典 金华[2,3] 王利蓉 WEI Qingdian;JIN Hua;WANG Lirong(The First Clinical Medical College of Anhui University of Traditional Chinese Medicine,Anhui Hefei 230000,China;The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Anhui Hefei 230000,China;Center for Xin’an Medicine and Modernization of Traditional Chinese Medicine of IHM,Anhui University of Traditional Chinese Medicine,Anhui Hefei 230000,China)

机构地区：[1]安徽中医药大学第一临床医学院,安徽合肥230000 [2]安徽中医药大学第一附属医院,安徽合肥230000 [3]合肥综合性国家科学中心大健康研究院,新安医学与中医药现代化研究所,安徽合肥230000

出　　处：《中医药临床杂志》2025年第2期333-339,共7页Clinical Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82274307);合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所专项资金(2023CXMMTCM018)。

摘　　要：目的:探讨清肾颗粒对腺嘌呤诱导肾纤维化大鼠的铁死亡及寡聚化结构域样受体蛋白3(NLRP3)炎症小体活性的影响作用。方法:构建腺嘌呤诱导肾纤维化大鼠模型,50只SD雄性大鼠分为正常组(Normal)、腺嘌呤组(Adenine)、清肾颗粒组(Qingshen Granules)、Liproxstatin-1组(LIP-1)、Liproxstatin-1空白组(LIP-1-NC),每组10只。Western blotting法检测肾组织中GPX4、NLRP3、IL-1β、IL-18蛋白表达;比色法检测肾组织中Fe^(2+)、Fe^(3+)含量;荧光探针法检测细胞内ROS荧光值;ELISA法检测细胞内GSH含量。Masson染色观察肾脏病理。结果:与正常组比较,腺嘌呤组大鼠的GPX4、GSH表达显著减少(P<0.05),NLRP3、IL-1β、IL-18表达及Fe^(2+)、Fe^(3+)含量均显著增加(P<0.05),肾脏病理可见纤维化改变和炎症细胞浸润。与腺嘌呤组比较,LIP-1组和清肾颗粒组大鼠的GPX4、GSH表达显著增加(P<0.05),NLRP3、IL-1β、IL-18表达和Fe^(2+)、Fe^(3+)含量减低(P<0.05),肾脏病理损害得到改善。结论:清肾颗粒可能通过上调GSH/GPX4的表达,抑制NLRP3炎症小体活化并下调炎症因子IL-1β、IL-18表达,减轻肾纤维化进程。Objective:To investigate the effect of Qingshen Granules on ferroptosis and NLRP3 inflammasome activity in rats with adenine-induced renal fibrosis.Methods:A rat model of adenine-induced renal fibrosis was constructed,and 50 SD male rats were divided into normal group(Normal),adenine group(Adenine),Qingshen Granules group(Qingshen Granules),Liproxstatin-1 group(LIP-1),and Liproxstatin-1-NC group(LIP-1-NC),with 15 rats in each group,a total of 5 groups.Western blotting was used to detect the protein expressions of GPX4,NLRP3,IL-1βand IL-18 in kidney tissue.Colorimetric method was used to detect the contents of Fe^(2+)and Fe^(3+)in kidney tissue.Fluorescent probe method was used to detect intracellular ROS fluorescence value.Intracellular GSH content was detected by ELISA.Masson staining was used to observe renal pathology.Results:Compared with the normal group,the expressions of GPX4 and GSH in adenine group decreased significantly(P<0.05),and the expressions of NLRP3,IL-1βand IL-18,as well as the contents of Fe^(2+)and Fe^(3+)were significantly increased(P<0.05),and renal pathology showed fibrotic changes and inflammatory cell infiltration.Compared with the adenine group,the expressions of GPX4 and GSH,NLRP3,IL-1β,IL-18 and Fe^(2+)were significantly increased in the LIP-1 group and the Qingshen Granules group(P<0.05),Fe^(3+)content decreased(P<0.05),and renal pathological damage was improved.Conclusion:Qingshen Granules may inhibit the activation of NLRP3 inflammasomes and down-regulate the expression of inflammatory factors IL-1βand IL-18 by up-regulating the expression of GSH/GPX4,and alleviate the process of renal fibrosis.

关 键 词：肾纤维化 清肾颗粒 铁死亡 寡聚化结构域样受体蛋白3小体 liproxstatin-1 

分 类 号：R-332[医药卫生]