西安交通大学学报（医学版）2025，Vol.46Issue(6)：947-952,6.DOI:10.7652/jdyxb202506008
雷公藤甲素通过抑制NLRP3介导的焦亡改善单侧输尿管梗阻小鼠肾间质纤维化
Triptolide ameliorates renal interstitial fibrosis in mice with unilateral ureteral obstruction by inhibiting NLRP3-mediated pyroptosis
摘要
Abstract
Objective To investigate the effect of triptolide(TPL)on renal interstitial fibrosis in mice with unilateral ureteral obstruction(UUO)and its mechanism.Methods Six male C57BL/6J mice were randomly selected as the sham group,and 12 mice with UUO modeling were randomly divided into the model group(UUO)and the triptolide group(TPL).Changes in serum creatinine(SCr),blood urea nitrogen(BUN),and body weight were compared among the groups.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.Immunohistochemistry staining was performed to observe the expression of α-smooth muscle actin(α-SMA)and fibronectin(Fn)in kidney tissues.Western blotting analysis was used to detect the protein expression levels of nucleotide combined with structure of oligomerization domain receptor protein 3(NLRP3),GSDMD,cGSDMD,IL-1β and IL-18.Results At week 1,the body weight of mice in the UUO and TPL groups significantly decreased compared with that in the sham group(P＜0.05).Body weight reduced in the TPL group compared with that in the Sham group at week 2(P＜0.01).There was no significant difference in body weight between the TPL and UUO groups.BUN levels did not differ significantly between the three groups.Compared with the sham group,the SCr level in the UUO group significantly increased[(15.680±1.508)μmol/L](P＜0.01).A reduction in SCr level was observed following TPL administration[(12.550±3.004)μmol/L](P＜0.05).HE staining showed that the renal tubules of mice in the UUO group were significantly dilated and atrophic,with interstitial edema and increased inflammatory cell infiltration,while the pathological damage of renal tissues was significantly alleviated after TPL treatment.Masson staining revealed that interstitial collagen deposition significantly increased in the UUO group(36.350±5.183)％(P＜0.01)and reduced after TPL administration(20.820±3.290)％(P＜0.01).Immunohistochemistry results demonstrated that the IOD levels of α-SMA(1.233±0.045)and Fn(1.337±0.045)were higher in UUO group mice than in the sham group,while the IOD levels of α-SMA(1.047±0.025)and Fn(1.113±0.021)were lower in the TPL group than in the UUO group(P＜0.05).Western blotting analysis indicated that the expression levels of NLRP3,cGSDMD,IL-1β and IL-18 in the UUO group mice were higher than those in the sham group,while the protein expression levels of the above-mentioned indicators significantly decreased after TPL treatment(P＜0.05).Conclusion TPL ameliorates renal interstitial fibrosis in mice with UUO by inhibiting NLRP3-mediated pyroptosis.关键词
雷公藤甲素/NOD样受体热蛋白结构域蛋白3(NLRP3)/单侧输尿管梗阻(UUO)/肾间质纤维化Key words
triptolide/NLRP3/unilateral ureteral obstruction(UUO)/renal interstitial fibrosis分类
临床医学引用本文复制引用
魏琳婷,葛蓬勃,李艳,李柯,王引红,赵纬昊,崔晨凯,付荣国..雷公藤甲素通过抑制NLRP3介导的焦亡改善单侧输尿管梗阻小鼠肾间质纤维化[J].西安交通大学学报（医学版）,2025,46(6):947-952,6.基金项目
国家自然科学基金资助项目(No.82170697,No.82405169),陕西省重点产业创新链(群)项目(No.2024SF-ZDCYL-03-05),陕西省自然科学基金资助项目(No.2022JM-472),中国医师协会医学循证专委会肾科学组PRO·润基金资助项目(No.KYJ202206-0003-3)Supported by the National Natural Science Foundation of China(No.82170697,No.82405169),Science and Technology Program of Shaanxi Province(No.2024SF-ZDCYL-03-05),Natural Science Foundation of Shaanxi Province(No.2022JM-472),and"PRO·Run"Fund of the Nephrology Group of CEBM(No.KYJ202206-0003-3) （No.82170697,No.82405169）
