二甲双胍通过调节血管外周脂肪细胞的累积抑制腹主动脉瘤的形成  

Metformin inhibiting formation of abdominal aortic aneurysm in mice via regulation of accumulating perivascular adipocytes

作　　者：田丽[1] 张瑾瑾 杨柳[1] 刘肖 叶春芳[1] 孟宪杰[1] 李会[1] 张丽华[1] 赵永波[3] 马冬 TIAN Li;ZHANG Jinjin;YANG Liu;LIU Xiao;YE Chunfang;MENG Xianjie;LI Hui;ZHANG Lihua;ZHAO Yongbo;MA Dong(Department of Endocrinology,Tangshan People′s Hospital,Tangshan,Hebei 063001,China;School of Public Health,North China University of Science and Technology,Tangshan,Hebei 063210,China;Department of Cardiac Surgery,the Fourth Affiliated Hospital of Hebei Medical University,Shijiazhuang,Hebei 050000,China)

机构地区：[1]河北省唐山市人民医院内分泌科,063001 [2]华北理工大学公共卫生学院,河北唐山063210 [3]河北医科大学附属第四医院心外科,石家庄050000

出　　处：《重庆医学》2022年第3期375-378,388,共5页Chongqing medicine

基　　金：国家自然科学基金项目(81700416)。

摘　　要：目的探讨二甲双胍抑制腹主动脉瘤(AAA)形成的作用机制。方法对10只8~10周龄ApoE-/-雄性小鼠高脂饮食并皮下植入含有血管紧张素Ⅱ的微量泵构建动脉瘤模型,均分为AAA组和二甲双胍干预组,4周后取材评估腹主动脉扩张情况,油红O染色观察血管外周脂肪细胞累积情况;免疫荧光染色和Western blot分析血管外周脂肪细胞的脂滴形成和缺氧诱导脂滴相关蛋白(HILPDA)的表达,qPCR检测血管外周脂肪组织中炎症因子的表达。结果与AAA组比较,二甲双胍抑制了血管外周脂肪细胞的累积并减少脂肪细胞脂滴的形成;Western blot和qPCR检测结果发现HILPDA及相关炎症因子[肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6]表达均降低(P<0.05)。结论二甲双胍可能通过调节HILPDA的表达减少血管外周脂肪细胞的累积和血管炎症,并最终抑制AAA的形成。Objective To explore the mechanism of metformin in inhibiting the formation of abdominal aortic aneurysm(AAA).Methods A total of ten ApoE-/-male mice aged eight to ten weeks were given a high fat diet and subcutaneously implanted with a mini pump containing angiotensinⅡfor building AAA model.All mice were averagely divided into the AAA group and the metformin intervention group.After four weeks,the abdominal aorta tissue was taken to evaluate the expansion.Oil red staining was performed to observe the accumulation of perivascular adipocytes(PAs).Subsequently,immunofluorescence staining and western blot were used to analyze the lipid droplet formation and the expression of hypoxia induced lipid droplet associated protein(HILPDA).Quantitative polymerase chain reaction(qPCR)was used to detect the expression of cytokines in PAs.Results Compared with the AAA group,the metformin intervention group inhibited the accumulation and reduced the formation of lipid droplets in PAs.Moreover,the results of Western blot and qPCR showed that the expression of HILPDA and cytokines(TNF-α,IL-1β,IL-6)was also decreased(P<0.05).Conclusion Metformin may reduce the accumulation of PAs and vascular inflammation by regulating the expression of HILPDA,contributing to inhibit the formation of AAA.

关 键 词：二甲双胍 腹主动脉瘤 血管外周脂肪细胞 HILPDA 炎症因子 

分 类 号：R363.2[医药卫生—病理学]