肿瘤坏死因子-α在慢性血栓栓塞性肺动脉高压大鼠模型肺血管重塑中的作用  

Role of TNF-α in vascular remodeling in rats with chronic thromboembolic pulmonary hypertension

作　　者：沈和平[1] 吴达文 陈云飞 连宁芳[2] 许昌声[2] 练桂丽 杨闽霞 邓朝胜[2] Shen Heping;Wu Dawen;Chen Yunfei;Lian Ningfang;Xu Changsheng;Lian Guili;Yang Minxia;Deng Chaosheng(Department of Basic Medicine,Zhangzhou Health Professional College,Zhangzhou 363000,China)

机构地区：[1]漳州卫生职业学院,363000 [2]福建医科大学附属第一医院呼吸科

出　　处：《中华结核和呼吸杂志》2018年第8期632-637,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金（81570264）;福建省中青年教师福建省中青年教师教育研究项目（JAT160911）

摘　　要：目的分析肿瘤坏死因子（TNF）－α与肺血管重塑的关系以探索CTEPH的发病机制。方法60只SD大鼠按照随机数字表法分为假手术组和实验组，每组30只，每组分为3个亚组：1、2、4周组，每组10只。经颈静脉反复注入自体血栓栓塞肺动脉，测量平均肺动脉压力（mPAP）。分别饲养1、2和4周后处死大鼠，分离肺动脉行组织病理学检查，检测血浆TNF－α浓度、肺动脉TNF－α蛋白质和抗原表达情况，分析其相关性。结果实验组中各亚组（1、2、4周）中实验组肺动脉TNF－α蛋白（1.62±0.08 vs 0.85 ±0.12、1.85±0.08 vs 0.89±0.13、1.37±0.12 vs 0.91±0.15）较假手术组明显升高（P〈0.05），血浆TNF－α浓度也有明显升高（P〈0.05）；mPAP和肺动脉管壁面积/管总面积（WA/TA）随着栓塞时间延长逐渐升高，且明显高于假手术组；免疫组化检测肺动脉内膜中TNF－α表达，实验组与假手术组比较表达升高；肺动脉TNF－α蛋白表达与mPAP呈正相关（r＝0.605，P〈0.01），并且与WA/TA表达呈正相关（r＝0.629，P〈0.01）；血浆TNF－α表达与肺动脉TNF－α蛋白表达呈正相关（r＝0.721，P〈0.01）。结论通过自体血栓反复多次栓塞，并给予纤溶抑制剂氨甲环酸可以建立较为理想的慢性血栓栓塞性肺动脉高压大鼠模型；血栓栓塞可诱发肺动脉内皮细胞TNF－α表达升高，并释放入血；TNF－α可能通过促进肺动脉血压升高和血管重塑参与CTEPH发病过程。ObjectiveTo analyze the relationship between TNF-α and pulmonary vascular remodeling in order to explore the pathogenesis of CTEPH.MethodsAutologous blood clots were repeatedly injected into the left jugular vein of rats to establish the CTEPH model. Then mean pulmonary artery pressure （mPAP）, histopathology, the plasma level of TNF-α, and the expressions of mRNA and protein of TNF-α in pulmonary artery were measured. ResultsIn the experiment group, the mPAP and vessel wall area/total area （WA/TA） ratio gradually increased as emblism extended, and increased significantly compared with the sham operation group. The plasma TNF-α concentration in the experimental group increased significantly （P〈0.05）. The TNF-α proteins expressed in pulmonary artery in the 1-week, 2-week, and 4-week subgroups of experimental group increased significantly compared with the sham operation group （1.62±0.08 vs 0.85±0.12, P〈0.05; 1.85±0.08 vs 0.89±0.13, P〈0.05; 1.37±0.12 vs 0.91±0.15, P〈0.05, respectively）. Immunohistochemical results showed that TNF-α expression was higher in pulmonary artery endothelial cells of the experimental group compared with the sham operation group. The expression of pulmonary artery TNF-α protein was positively related with mPAP （r=0.605, P〈0.01）, and with WA/TA （r=0.629, P〈0.01）. The expression of serum TNF-α was positively related with that of pulmonary artery TNF-α protein （r=0.721, P〈0.01）.ConclusionA rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. Thrombosis induced higher expression of TNF-α in pulmonary arterial endothelial cells, and released into the blood. TNF-α may play an important role in the development of CTEPH, especially by contributing to vascular remodeling and PH.

关 键 词：高血压 肺性 TNF-α 动物模型 血管重塑 

分 类 号：R544.1[医药卫生—心血管疾病] R-332[医药卫生—内科学]