南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (2): 317-323.doi: 10.12122/j.issn.1673-4254.2024.02.14

• • 上一篇    下一篇

绿原酸减轻脓毒症诱导的小鼠急性肾损伤：基于抑制caspase-1经典细胞焦亡信号通路

房尚萍，孙任珂，苏 慧，翟科程，项 毓，高杨梦娜，郭文俊   

  1. 皖南医学院麻醉学院，麻醉学实验实训中心，第一附属医院，安徽 芜湖 241002
  • 发布日期:2024-03-13

Chlorogenic acid alleviates acute kidney injury in septic mice by inhibiting NLRP3 inflammasomes and the caspase-1 canonical pyroptosis pathway

FANG Shangping, SUN Renke, SU Hui, ZHAI Kecheng, XIANG Yu, GAO Yangmengna, GUO Wenjun   

  1. School of Anesthesiology, Laboratory and Training Center of Anesthesiology, First Affiliated Hospital, Wannan Medical College, Wuhu 241002, China
  • Published:2024-03-13

RichHTML

4

PDF

73

摘要： 目的 探讨caspase-1经典的细胞焦亡信号通路在绿原酸治疗急性肾损伤小鼠中的作用及机制。方法 将24只C57Bl/6J小鼠随机分成4组，每组6只：假手术组（Sham组）、盲肠结扎穿刺组（CLP组）、CLP+地塞米松组（CLP+DXM组）、CLP+绿原酸组（CLP+CGA组）。Sham组小鼠仅开腹未造模，CLP组CLP+DXM组和CLP+CGA组小鼠均盲肠结扎穿刺（CLP）造模。Sham组、CLP组、CLP+DXM组和CLP+CGA组在造模后持续静脉泵注生理盐水10 mg/kg、生理盐水10 mg/kg，注地塞米松1 μg/kg和绿原酸15 mg/kg 6 h。各组均在注射药物结束后8 h，比较各组小鼠7 d生存率，肾组织大体形态、HE染色，肾组织细胞凋亡及肾功能相关指标尿素氮（BUN）、肌酐（Scr）、肾损伤分子1（KIM-1）；及肾组织NLRP3炎性小体和caspase-1通路关键蛋白表达情况。结果 绿原酸干预后提高了小鼠7 d生存率，肾组织肾小球毛细血管充血、肾间质水肿、肾小管上皮细胞肿胀程度明显减轻（P<0.05），降低了肾功能指标BUN、Scr、KIM-1水平；NLRP3炎性小体及caspase-1通路关键蛋白表达。结论 绿原酸可能通过抑制NLRP3炎性小体和caspase-1信号通路，改善盲肠结扎穿刺所致急性肾损伤。

关键词: 绿原酸；急性肾损伤；脓毒症；细胞焦亡；NLRP3炎性小体

Abstract: Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid (CGA) treatment of acute kidney injury (AKI) in mice. Method Twenty-four C57Bl/6J mice were randomized into sham-operated group, cecal ligation and puncture (CLP) group, CLP+dexamethasone group (CLP+DXM group), and CLP+CGA group (n=6) and subjected to either sham operation (laparotomy only) or CLP. After modeling the mice received intravenous infusion of 10 mg/kg normal saline (in sham and CLP groups), 1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump. Eight hours after the infusion, renal morphology and histology, renal cell apoptosis, and the renal function parameters such as urea nitrogen (BUN), creatinine (Scr), and kidney injury molecule 1 (KIM-1) were compared among the 4 groups; the 7-day survival rates of the mice were recorded, and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected. Results CGA treatment significantly improved the 7-day survival rate, reduced renal pathologies of the septic mice (P<0.05), and lowered the levels of BUN, Scr, KIM-1, NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway. Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Key words: chlorogenic acid; acute kidney injury; sepsis; cell pyroptosis; NLRP3 inflammasomes