摘要： 目的 探讨丹皮酚对大鼠肾缺血再灌注损伤（RIRI）的作用及其机制。方法 将30只SD大鼠随机分为假手术组（Sham组）、模型组（RIRI组）、丹皮酚组（Pae组）、TLR4抑制剂组（TAK242组）及丹皮酚+TLR4抑制剂组（Pae+TAK242组），每组6只。缺血（45 min）再灌注（24 h）损伤模型成功建立后检测各组大鼠血清肌酐（Scr）、血尿素氮（BUN）、胱抑素C （CysC）水平，ELISA检测血清中IL-1β和IL-18水平，HE染色观察各组肾脏组织形态学变化，免疫组化检测肾脏组织中TLR4、MyD88、IL-1β、IL-18、caspase 1表达及分布，Western blotting检测TLR4、MyD88、细胞焦亡相关蛋白NOD样受体蛋白3 （NLRP3）、caspase 1、Gasdermin D （GSDMD）、IL-1β、IL-18蛋白表达水平。结果 与Sham组比较，RIRI组Scr、Bun及CysC水平升高（均P < 0.05），肾组织损伤较重，炎性细胞因子IL-1β、IL-18水平升高（均P < 0.05），NLRP3、caspase 1、GSDMD、IL-1β、IL-18蛋白表达均升高（均P < 0.05）。与RIRI组比较，Pae组、TAK242组和Pae+TAK242组Scr、Bun及CysC水平均下降（均P < 0.05），肾组织损伤均较轻，IL-18、IL-1β水平均降低（均P < 0.05），TLR4、MyD88、NLRP3、caspase 1、GSDMD、IL-1β、IL-18蛋白表达均下降（均P < 0.05）。结论 丹皮酚可减轻RIRI，其机制可能是通过抑制TLR4-MyD88-NLRP3通路，从而抑制细胞焦亡实现的。

丹皮酚对大鼠肾缺血再灌注损伤的作用及其机制

申开文^1,2, 张瑞波¹, 王强¹, 袁强¹, 沈俊¹

1. 贵州医科大学附属医院泌尿外科, 贵阳 550004;
2. 中山大学附属第一医院贵州医院泌尿外科, 贵阳 550000

收稿日期:2022-12-20出版日期:2023-11-30发布日期:2023-11-07
通讯作者:沈俊E-mail:shenjun@gmc.edu.cn
作者简介:申开文(1995-),男,医师,硕士研究生.
基金资助:贵州省卫生健康委科学技术基金（gzwkj2021-220）；贵州医科大学附属医院博士科研启动基金（gyfybsky-2022-31）；贵州医科大学附属医院国家自然科学基金培育项目［gyfynsfc（2020）-30）］


关键词: 丹皮酚, 肾缺血再灌注损伤, 大鼠
Abstract: Objective To investigate the effect and mechanism of paeonol on renal ischemia-reperfusion injury (RIRI) in rats. Methods Thirty SD rats were randomly divided into sham, model (RIRI), paeonol (Pae), TLR4 inhibitor (TAK242), and Pae+TAK242 groups, with six rats in each group. After the ischemia (45 min) reperfusion (24 h) injury model had successfully been established, serum creatinine (Scr), blood urea nitrogen (BUN), and Cystatin C (CysC) levels were recorded. Serum IL-1β and IL-18 levels were detected using enzyme linked immunosorbent assay. Renal histopathologic changes in each group were observed after HE staining. The expression and distribution of TLR4, MyD88, IL-1β, IL-18, and caspase 1 in kidney tissues were detected by immunohistochemistry. Western blotting revealed the expression levels of TLR4, MyD88, NOD-like receptor protein 3 (NLRP3), caspase 1, Gasdermin D (GSDMD), IL-1β, and IL-18. Results Compared to the sham group, the RIRI group showed higher levels of Scr, BUN, and CysC (all P < 0.05), more serious renal tissue damage, and elevated levels of inflammatory cytokines IL-1β and IL-18 (all P < 0.05). The protein expressions of NLRP3, caspase 1, GSDMD, IL-1β, and IL-18 also increased (all P < 0.05). Compared to the RIRI group, the Pae, TAK242, and Pae+TAK242 groups showed reduced levels of Scr, BUN, and CysC (all P < 0.05), less severe renal tissue injury, decreased levels of IL-18 and IL-1β (all P < 0.05), and reduced expressions of TLR4, MyD88, NLRP3, caspase 1, GSDMD, IL-1β, and IL-18 (P < 0.05). Conclusion Paeonol alleviated RIRI by inhibiting pyroptosis through the TLR4-MyD88-NLRP3 pathway.
Key words: paeonol, renal ischemia reperfusion injury, rat
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