芦丁对小鼠脓毒症多器官功能障碍的作用与机制研究  

The mechanism of Rutin on multiple organ dysfunction induced by sepsis in mice

作　　者：晏竹林 吴伏鹏 李海东[1] YAN Zhu-lin;WU Fu-peng;LI Hai-dong(Department of Emergency,Minhang Hospital,Fudan University,Shanghai 201199,China)

机构地区：[1]复旦大学附属闵行医院急诊科,上海201199

出　　处：《复旦学报(医学版)》2025年第2期232-241,共10页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金青年项目(82302420);上海市卫健委科研课题青年项目(20234Y0227)。

摘　　要：目的探究芦丁对脓毒症小鼠多器官损伤的影响并从炎症角度探究其机制。方法雄性C57BL/6小鼠分为正常对照组(sham)、盲肠结扎穿孔(cecal ligation and puncture,CLP)组、芦丁低剂量(25 mg/kg)组、芦丁中剂量(50 mg/kg)组和芦丁高剂量(100 mg/kg)组,每组20只。所有小鼠8周龄时开始每天灌胃给药7天(芦丁各剂量组给予对应剂量的药物,sham组和CLP组给予相同体积的生理盐水),随后通过CLP诱导小鼠脓毒症。分析小鼠生存率;通过HE染色分析小鼠肺、肝、肾病理损伤;测量小鼠肺系数与肺湿干重(wet/dry,W/D)比;检测小鼠血清中谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、血肌酐(creatinine,CRE)、尿素氮(urea nitrogen,BUN)含量;检测小鼠尿蛋白含量;RT-qPCR检测小鼠组织肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、IL-6的mRNA水平;Western blot分析JAK2-STAT3信号通路的活化情况。结果芦丁降低脓毒症小鼠的死亡率,减轻其肝、肺、肾损伤并改善肝、肺、肾功能,抑制组织JAK2-STAT3信号通路的活化并减少促炎因子的mRNA表达。结论芦丁可能通过抑制JAK2-STAT3信号通路的活化减轻炎症,对脓毒症小鼠的肝、肺、肾损伤具有保护作用。Objective To explore the effects of Rutin on multiple organ damage in septic mice and to investigate its mechanism from the perspective of inflammation.Methods Male C57BL/6 mice were divided into the normal control(sham)group,cecal ligation and puncture(CLP)group,low-dose Rutin group(25 mg/kg),medium-dose Rutin group(50 mg/kg),and high-dose Rutin group(100 mg/kg),there are 20 mouse in each group.All mice were given gavage daily for 7 days starting at 8 weeks of age(the Rutin groups were administered the corresponding doses of the drug,while the sham and CLP groups were given the same volume of saline).Subsequently,sepsis was induced in mice by CLP.The survival rate of mice was analyzed;pathological damage of the lungs,liver,and kidneys in mice was assessed by HE staining;the lung coefficient and wet/dry(W/D)ratio of the lungs were measured;the levels of alanine transaminase(ALT),aspartate aminotransferase(AST),creatinine(CRE),and urea nitrogen (BUN)in mouse serum were detected;the content of urinary protein in mice was measured;the mRNA levels of tumor necrosis factor-α(TNF-α)and IL-6 in mouse tissues were detected by RT-qPCR;and the activation of the JAK2-STAT3 signaling pathway was analyzed by Western blot.Results Rutin reduced the mortality rate of septic mice,alleviated liver,lung,and kidney damage,improved liver,lung,and kidney functions,inhibited the activation of the JAK2-STAT3 signaling pathway in tissues,and reduced the mRNA expression of pro-inflammatory factors.Conclusion Rutin may alleviate inflammation by inhibiting the activation of the JAK2-STAT3 signaling pathway,and has a protective effect on liver,lung,and kidney damage in septic mice.

关 键 词：芦丁 脓毒症 多器官功能障碍 炎症 小鼠 

分 类 号：R631.2[医药卫生—外科学]