老年大鼠心肌组织Toll样受体4的激活在脑心综合征中的作用

The role myocardial Toll like receptor-4 activation in pathogenesis of cerebral-cardiac syndrome in aged rats

目的探讨老年大鼠心肌组织Toll样受体4（Toll like receptor4，TLR4）的激活与急性脑缺血再灌注继发心肌损伤的关系。方法线栓法制造局灶性脑缺血再灌注损伤大鼠模型，采用免疫组织化学法观察TLR4不同再灌注时间点心肌组织的表达，同时监测不同再灌注时间点大鼠心电图的改变和肌酸激酶同工酶MB（creatine-kinase isoenzyme MB，CK—MB）浓度的变化，并分析其与心肌TLR4表达相关性。结果实验大鼠大脑中动脉阻塞后，心电图异常的发生率为77．5％（31／40），且以ST-T改变为主；与对照组比较，在脑缺血再灌注3hCK—MB水平[分别为（179．6±22．5）IU／L与（302．6±39．3）IU／L，P〈0．05]开始升高，于再灌注12h达峰值[（481．4±52．2）IU／L，P〈0．01]；心肌TLR4蛋白在大鼠脑缺血再灌注3h即观察到少量表达，6h表达达到高峰，与假手术组比较，差异有统计学意义（分别为3．00±0．82、7．86±1．35和1．00±0．58，均为P〈0．01），且表达量与CK—MB浓度变化呈正相关（r=0．642，P〈0．01）。结论心肌TLR4受体在老年大鼠脑缺血再灌注对心肌损伤过程中被激活，可能与心肌受损有关，提示炎症反应有可能是脑心综合征发病机制中的一个重要环节．

Objective To explore the relation between activation of myocardial Toll like receptor-4（TLR4） and cerebral-cardiac syndrome（CCS） in aged rats. Methods The model of acute cerebral ischemia-reperfusion in aged rats was established with the suture-occluded method invented by ZeaLonga. The changes of creatine-kinase isoenzyme MB（CK-MB） and electrocardiogram （ECG） were monitored and myocardium TLR4 level was determined by immunohistochemistry. Results The occurrence rate of abnormal electrocardiogram（ECG） was 77.5 % （31/40） after the middle cerebral artery（MCA） was occluded, and the main ECG abnormities were the changes of ST-T. Compared with the control group, the level of CK-MB [in model group（179.6±22.5）IU/L vs. （302.6±39.3） IU/L, P〈0. 05] increased significantly in 3 hours and reached peak at 12 hours after reperfusion[（481.4± 52.2） IU/L]. After 3 hours ischemia the expression of TLR4 protein increased and reached peak 12 hours after reperfusion. And the expression of myocardial TLR4 was positively correlated with the level of CK-MB（r= 0. 642,P〈0. 01）. Conclusions Myocardial TLR4 activation in the process of partial cerebral ischemia-reperfusion with cardiac injury plays a role in the mechanism of CCS.