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|本期目录/Table of Contents|

川崎病致肺动脉内皮损伤和肺动脉高压的实验研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第3期
页码:
264-269
栏目:
基础研究
出版日期:
2018-03-25

文章信息/Info

Title:
Pulmonary artery endothelial injury and pulmonary hypertension induced by Kawasaki disease
作者:
石曌玲1; 2; 刘曼玲3; 马 恒1; 3
（第四军医大学：1.基础医学院生理学教研室，2.西京医院小儿科，3.基础医学院病理生理学教研室,陕西 西安 710032)
Author(s):
SHI Zhao-ling1; 2;  LIU Man-ling3;  MA Heng1; 3
(1.Department of Physiology, 3.Department of Pathophysiology, School of Basic Medical Science; 2.Department of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
川崎病; 内皮细胞损伤; 氧化应激; 肺动脉高压
Keywords:
Kawasaki disease;  endothelium injury;  oxidative stress;  pulmonary arterial hypertension
分类号:
R725.4
DOI:
-
文献标识码:
A
摘要:
目的 探讨川崎病(KD)对肺血管内皮功能的影响以及与肺动脉高压发生的相关性。方法 采用干酪乳杆菌细胞壁成分(LCWE)建立川崎病大鼠模型，将40只(1月龄)SD大鼠随机分为对照组和KD组，KD组大鼠腹腔注射LCWE 0.5 ml(1 mg/ml)来建造KD模型。造模2周后采用组织病理学评估冠状动脉和肺动脉的损伤情况。测定大鼠体循环压力、右心室压力和右心室肥厚指数、肺小动脉舒张功能。检测肺小动脉组织抗氧化酶锰超氧化物歧化酶(MnSOD)和过氧化氢酶(Catalase)的表达水平，以及氧化应激水平。结果 LCWE注射14 d后，与对照组比较，成功诱导KD大鼠冠状动脉损伤(P<0.05)，KD组大鼠出现肺组织损伤，肺组织水肿，点、片状出血，伴中性粒细胞为主的炎性细胞浸润。肺小动脉内皮细胞肿胀，中膜层出现不规则间断性肥厚，管腔呈部分狭窄，肺动脉损伤评分升高(P<0.05)。肺小动脉组织MnSOD和Catalase的表达水平较对照组显著降低(P<0.05)，髓过氧化物酶(MPO)、丙二醛(MDA)水平明显升高(P<0.05)。同时，KD组大鼠右心室压力和肥厚指数较对照组明显升高(P<0.05)，离体血管灌流实验证实，KD组大鼠肺小动脉内皮依赖性的舒张作用明显减弱(P<0.01)。结论 KD可导致肺小动脉血管炎，引发肺小动脉血管内皮损伤和氧化应激损伤，可能是诱发肺动脉高压和继发性心脏损伤的重要原因之一。
Abstract:
AIM To investigate the effects of Kawasaki disease (KD) on pulmonary vascular endothelial function and to evaluate any correlation with pulmonary hypertension. METHODS Forty rats (1 month old) were randomly divided into a control group and a KD group. The rats in the KD group were intraperitoneally injected with lactobacillus casei cell wall extract (LCWE) 0.5 ml (1 mg/ml). Two weeks after modeling, coronary artery and pulmonary artery injury were histopathologically assessed. Blood pressure, right ventricular pressure, right ventricular hypertrophy index and pulmonary artery diastolic function were measured. The levels of antioxidant enzymes MnSOD, Catalase and oxidative stress were measured in pulmonary arterioles. RESULTS After 14 days of LCWE injection, coronary artery injury in the KD rats was successfully induced (P<0.05). On this basis, it was demonstrated that KD rats had lung injury, pulmonary edema, point/flaky hemorrhage, and neutrophil-like inflammatory cell infiltration. Pulmonary arterial endothelial cells were swollen, irregular intermittent hypertrophy appeared in the middle layer, and the lumen was partially narrowed and the pulmonary artery injury score increased (P<0.05). It was revealed that levels of MnSOD and Catalase in pulmonary arterioles were significantly lower than those in the control group (P<0.05), while levels of MPO and MDA in oxidative stress were significantly increased (P<0.05). The right ventricular pressure and hypertrophy index of the KD rats were significantly increased (P<0.05). In vitro vascular perfusion experiments confirmed that pulmonary arterial endothelium-dependent relaxation effect was significantly reduced in KD rats (P<0.01). CONCLUSION In addition to known coronary damaging effects, Kawasaki disease can lead to pulmonary arteritis, causing pulmonary arterial vascular injury and oxidative stress injury, which may potentially induce pulmonary hypertension and secondary heart injury.

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备注/Memo

备注/Memo:
收稿日期：2017-10-26.基金项目：国家自然科学基金资助（31671424，81200036）；陕西省社发攻关项目资助（2011KJXX66，2015KW-050） 通讯作者：马恒，副教授，主要从事心肺损伤机制研究 Email:hengma@fmmu.edu.cn 共同通讯作者：刘曼玲，讲师，博士，主要从事肺动脉高压致病机制研究 Email:apple0210vip@163.com 作者简介：石曌玲，主治医师，博士生 Email：21858868@qq.com
更新日期/Last Update: 1900-01-01