Regulatory T cells contribute to rosuvastatin-induced cardioprotection against ischemia-reperfusion injury
Regulatory T cells contribute to rosuvastatin-induced cardioprotection against ischemia-reperfusion injury
复制标题
调节性 T 细胞有助于瑞舒伐他汀诱导的针对缺血再灌注损伤的心脏保护作用
DOI：
10.1097/mca.0b013e3283608c12
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发表时间：
2013-06-01
影响因子：
1.8
通讯作者：
Chen, Lianglong
中科院分区：
文献类型：
--
作者：
Ke, Dan;Fang, Jun;Chen, Lianglong
目的CD 4（+）CD 25（+）调节性T细胞（Treg）通过抑制免疫反应在预防各种炎症和自身免疫性疾病中发挥关键作用。他汀类药物对心肌缺血再灌注损伤（IRI）的有益作用部分取决于其免疫调节和抗炎机制。方法32只大鼠随机分为假手术组、缺血再灌注组（IR）、瑞舒伐他汀（RSV）/IR组和甲羟戊酸（MVA）+ RSV/IR组。再灌注前18 h静脉注射RSV（5 mg/kg），再灌注48 h后处死大鼠。ELISA法检测血清心肌肌钙蛋白I（cTnI）水平，苏木精-伊红染色法检测心肌组织炎症细胞浸润，Western blotting法检测FoxP 3蛋白的表达，免疫组化法检测心肌组织中凝血酶的蓄积，TTC染色法检测梗死面积。与IR组相比，RSV治疗组血清cTnI水平明显降低，炎症细胞聚集减少，梗死面积缩小，心肌组织FoxP 3表达和Treg聚集增加。RSV和MVA联合预处理可部分消除RSV诱导的抗炎和梗死面积限制作用，并完全逆转RSV诱导的Treg在心肌中的积聚。结论呼吸道合胞病毒预处理可增加Treg的表达，减轻炎症反应，减轻心肌损伤，提示呼吸道合胞病毒预处理对IRI的心肌保护作用可能是通过HMG-CoA还原酶途径介导的Treg负性调节炎症反应。科龙动脉病变24：334-341（c）2013年沃尔特斯·克鲁沃健康垂直酒吧利平科特威廉姆斯和威尔金斯。
Objectives CD4(+) CD25(+) regulatory T cells (Tregs) play a key role in the prevention of various inflammatory and autoimmune disorders by suppressing immune responses. The beneficial effect of statins on myocardial ischemia-reperfusion injury (IRI) depends in part on their immunomodulatory and anti-inflammatory mechanisms. We aimed to determine whether Tregs contribute to statin-induced cardioprotection against myocardial IRI.Methods Thirty-two rats were divided into four groups: sham, ischemia-reperfusion (IR), rosuvastatin (RSV)/IR, and mevalonic acid (MVA) + RSV/IR. Myocardial IR was induced by a 30-min coronary occlusion, followed by a 48-h reperfusion. RSV (5 mg/kg) was administered intravenously 18 h before IR. The rats were killed after 48-h reperfusion. Serum cardiac troponin I (cTnI) was measured by ELISA, infiltration of inflammatory cells in myocardium by hematoxylin and eosin staining, expression of FoxP3 protein by western blotting, accumulation of Tregs in myocardium by immunohistochemical examination, and infarct size by TTC staining.Results Significant elevation in serum cTnI, enlarged infarct size, and marked infiltration of inflammatory cells in myocardium were observed in the IR group. The administration of RSV significantly reduced the serum cTnI level, attenuated the accumulation of inflammatory cells, decreased infarct size, and increased the FoxP3 expression and Treg accumulation in myocardium compared with the IR group. The combination of RSV and MVA pretreatment partially abolished the anti-inflammatory and infarct size-limiting effects and completely reversed Treg accumulation in myocardium induced by RSV. The accumulation of inflammatory cells was negatively correlated with FoxP3 expression and Treg accumulation in the ischemic myocardium.Conclusion RSV pretreatment was associated with more Treg accumulation, less inflammatory response, and myocardial injury, suggesting that such cardioprotection against IRI was partially mediated by Treg-negative modulation of inflammation response, probably through the HMG-CoA reductase pathway. Coron Artery Dis 24:334-341 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.