2024 年第 3 期 第 19 卷

橘皮素通过腺苷酸激活蛋白激酶/哺乳动物雷帕霉素靶蛋白信号通路调控细胞自噬促进大鼠腹主动脉瘤发生发展的机制

The mechanism of tangerine regulating autophagy and promoting the occurrence and development of abdominal aortic aneurysm in rats based on adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway

作者：王大鹏1冯玉婧2张硕1任庆帅1裴建军1赵长全1

英文作者：Wang Dapeng1 Feng Yujing2 Zhang Shuo1 Ren Qingshuai1 Pei Jianjun1 Zhao Changquan1

单位：1华北理工大学附属医院心脏血管外科，唐山063000；2开滦总医院神经内科一病区，唐山063000

英文单位：1Department of Cardiovascular Surgery North China University of Science and Technology Affiliated Hospital Tangshan 063000 China; 2Department of Neurology Ward One Kailuan General Hospital Tangshan 063000 China

关键词：腹主动脉瘤；腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白信号通路；橘皮素

英文关键词：Abdominalaorticaneurysm;Adenosinemonophosphate-activatedproteinkinase/mammaliantargetofrapamycinsignalingpathway;Tangerine

• 摘要：

• 目的 探讨橘皮素通过腺苷酸激活蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路调控细胞自噬促进大鼠腹主动脉瘤（AAA）发生发展的机制。方法 选取无特定病原体级SD雌性大鼠45只，其中20只大鼠皮下埋植0.9%氯化钠注射液缓释泵（对照组），剩余25只大鼠皮下埋植血管紧张素Ⅱ缓释泵（AAA组）构建AAA模型。造模过程中AAA组大鼠死亡5只，共20只造模成功。对照组予0.9%氯化钠注射液灌胃，AAA组予橘皮素灌胃1次/d，持续7 d。观察大鼠主动脉血管平滑肌细胞活力、细胞凋亡率、细胞迁移率，比较2组细胞蛋白水平、自噬细胞基因表达量、细胞因子水平及AMPK/mTOR信号通路表达量。结果 AAA组细胞活力高于对照组，细胞凋亡率、细胞迁移率均低于对照组（均P＜0.05）；β-连环蛋白、B淋巴细胞瘤2（Bcl-2）相关X蛋白水平均低于对照组，细胞周期蛋白D1、Bcl-2水平均高于对照组（均P＜0.05）；Beclin1、Atg4b、Bnip3、Vps34、LC3基因表达量均低于对照组（均P=0.001）；白细胞介素6、正常T淋巴细胞表达和分泌的细胞因子、转化生长因子β、胰岛素样生长因子1、单核细胞趋化蛋白1水平均低于对照组（均P<0.05）；AMPK、mTOR表达量均高于对照组［（1.61±0.35）比（1.10±0.21）、（2.11±0.14）比（1.13±0.06）］（均P=0.001）。结论 橘皮素对AAA大鼠细胞蛋白水平、自噬细胞水平及转化生长因子水平有调节作用，其作用机制可能与AMPK/mTOR信号通路调控相关。

• Objective To explore the mechanism of tangerine regulating autophagy and promoting the occurrence and development of abdominal aortic aneurysm(AAA) in rats based on adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway. Methods Totally 45 female SD rats with specific pathogen-free grade were selected. Of which 20 rats were subcutaneously implanted with 0.9% sodium chloride injection sustained-release pumps(control group), and the remaining 25 rats were subcutaneously implanted angiotensin Ⅱ sustained-release pumps(AAA group) to build AAA model. During the modeling process, 5 rats in the AAA group died, and a total of 20 rats were successfully modeled. The control group was given 0.9% sodium chloride injection intragastric administration and the AAA group was given tangerine intragastric administration once a day for 7 d. The aortic vascular smooth muscle cell viability, cell apoptosis rate, and cell migration rate of rats were observed. The cell protein level, autophagy cell gene expression and cell factor level, and AMPK/mTOR signaling pathway expression of the two groups were compared. Results The cell viability in the AAA group was higher than that in the control group, and the cell apoptosis rate and cell migration rate were lower than those of control group (all P＜0.05). The levels of β-catenin and B cell lymphoma 2 (Bcl-2) associated X protein were lower than those in the control group, and the levels of cyclin D1 and Bcl-2 were higher than those in the control group(all P<0.05). The gene expressions of Beclin1, Atg4b, Bnip3, Vps34 and LC3 were lower than those in the control group (all P=0.001).The levels of interleukin-6, cytokines expressed and secreted by normal T lymphocytes, transform growth factors-β, insulin-like growth factor-1 and monocytes chemotactic proteins-1 were lower than those in the control group (all P<0.05), and the expressions of AMPK and mTOR were higher than those in the control group ［（1.61±0.35） vs （1.10±0.21）,（2.11±0.14） vs （1.13±0.06）］(both P=0.001). Conclusions  Tangeretin has an ameliorative effect on the levels of cell protein level, autophagy level and transforming growth factor level inAAA rats, and its mechanism may be associated with the regulation of AMPK/mTOR signaling pathways.