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自噬相关基因5下调抑制静脉桥血管狭窄

Down-regulation of autophagy-related gene 5 inhibits venous bridge stenosis

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【作者】 赵伟石洪涛刘瑞超郑娇杜杰张海滨陈晨

【Author】 Zhao Wei;Shi Hongtao;Liu Ruichao;Zheng Jiao;Du Jie;Zhang Haibin;Chen Chen;Department of Cardiology,Beijing Luhe Hospital,Capital Medical University;Department of Cardiology, Zhongshan Hospital,Fudan University;Depertment of Obstetrics and Gynecology, The People’s Hospital of Renqiu City;Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,Beijing Institute of Heart Lung and Blood Vessel Diseases;China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University;

【通讯作者】 陈晨;

【机构】 首都医科大学附属北京潞河医院心内科复旦大学附属中山医院心内科河北省任丘市人民医院妇产科首都医科大学附属北京安贞医院,北京市心肺血管疾病研究所,教育部重塑相关心血管疾病重点实验室首都医科大学附属北京潞河医院,中美神经科学研究所

【摘要】 目的探讨自噬相关基因5(Atg5)在小鼠下腔静脉移植术后静脉桥血管狭窄过程中的作用。方法 30只雄性C57BL/6小鼠及20只Atg5+/-小鼠分为WT假手术组(10只),WT手术组(受体10只,供体10只),Atg5+/-手术组(受体10只,供体10只)。复制小鼠下腔静脉移植模型。HE染色观察下腔静脉管腔面积,Real-time PCR检测下腔静脉组织中Atg5、LC3 mRNA表达;Westem-Blot检测下腔静脉组织中Atg5、LC3蛋白表达,免疫荧光共染明确平滑肌细胞中LC3表达。结果 WT小鼠下腔静脉移植4周后出现管腔狭窄[(4.21±0.32)×104μm2比(1.63±0.15)×104μum2,P<0.05],Atg5[(0.51±0.17)×10-3 比(1.49±0.08)×10-3]、LC3[(1.9±0.4)×10-2 比(3.8±0.9)×10-2] mRNA表达均明显升高(均为P<0.05)。与WT小鼠相比,Atg5+/-小鼠下腔静脉移植4周后Atg5[(0.39±0.05)比(0.16±0.08)]、LC3[(2.17±0.46)比(0.78±0.19)]蛋白表达均明显下降(均为P<0.05),平滑肌细胞中LC3蛋白表达显著下降(P<0.05),管腔狭窄明显减轻[(1.63±0.15)×104μm2比(2.96±0.12)×104μm2,P<0.05]。结论 Atg5下调抑制小鼠下腔静脉移植术后静脉桥血管狭窄。

【Abstract】 Objective To determinate the role of autophagy-related gene 5(Atg5) in the stenosis of vein graft after inferior vena cava transplantation in mice. Methods Thirty male C57 BL/6 wild type mice and 20 Atg5+/- mice were divided randomly into into a WT sham operation group(n=10), a WT surgery group(10 recipients, 10 donors), and an Atg5+/- surgery group(10 recipients, 10 donors). HE staining was used to detect the stenosis of vein graft. The mRNA level of Atg5 and LC3 was detect by Real-time PCR. The protein of Atg5 and LC3 were measured by Westem-Blot. Immunofluorescence was used to analyze the specific cell type. Results The lumen of vein grafts in Atg5+/- mice at 4 weeks after the inferior vena cava transplantation was wider than that in WT mice [(4.21±0.32)×104 μm2 vs.(1.63±0.15) ×104 μm2,P<0.05], with increased Atg5 [(0.51±0.17)×10-3 vs.(1.49±0.08)×10-3], LC3[(1.9±0.4)×10-2 vs.(3.8±0.9)×10-2] mRNA expression in vein graft of WT mice(all P < 0.05). Compared with the WT mice, there were significant less Atg5 [(0.39±0.05) vs.(0.16±0.08)], LC3[(2.17±0.46) vs.(0.78±0.19)] in vein graft of Atg5+/- mice(all P < 0.05). Similarly, the expression of LC3 in smooth muscle cells of Atg5+/- vein graft was significantly decreased(P<0.05), and the lumen of vein graft in Atg5+/- mice was significantly decreased than that in WT mice [(1.63±0.15) ×104 μm2 vs.(2.96±0.12)×104 μm2, P<0.05]. Conclusions Our results demonstrate that Atg5 deficiency inhibited the stenosis of vein graft.

【基金】 北京市自然科学基金项目(7194281)~~
  • 【文献出处】 中国心血管杂志 ,Chinese Journal of Cardiovascular Medicine , 编辑部邮箱 ,2020年01期
  • 【分类号】R654.2
  • 【下载频次】55
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