胸腺素β4对大鼠局灶性脑缺血再灌注损伤后血脑屏障的影响

摘要

Objective To determine the effect of thymosin β4 on blood-brain barrier ( BBB) after focal cerebral ische-mia and reperfusion injuries in rats , and to explore the mechanism .Methods Seventy-two SD rats were randomly divided into 3 groups:sham operation group (n=24), control group (n=24) and thymosin β4 group (n=24).Focal cerebral is-chemia and reperfusion rat models were made by using the method of thread inserting middle cerebral artery occlusion ( MCAO) , and the brain water content of ischemic tissues was measured 24 h after reperfusion by using the dry-wet weight method.At the same time, the permeability of blood-brain barrier was observed by detecting the content of Evans blue leaked out the brain tissue of ischemic side .The expression of tight junction protein Claudin-5 and matrix metalloproteinase-9 ( MMP-9) mRNA in ischemic brain tissues was detected by RT-PCR.Results Twenty-four hours after cerebral ische-mia and reperfusion injuries , the content of brain water of ischemic side , Evans blue content of ischemic side , and the ex-pression of MMP-9 mRNA significantly increased in the control group as compared with those of the sham-operation group , but the expression of Claudin-5 mRNA decreased significantly .However , the content of brain water of ischemic side , Evans blue content of ischemic side , and the expression of MMP-9 mRNA significantly decreased in the thymosin β4 group as compared with those of the control group , and the expression of Claudin-5 mRNA increased significantly (all P<0.05). Conclusion Thymosin β4 has the protective effect on BBB after cerebral ischemia and reperfusion injuries of rats , whose mechanism may be related to increasing the expression of tight junction protein Claudin -5 mRNA and decreasing the expres-sion of MMP-9 mRNA.%目的：观察胸腺素β4对大鼠局灶性脑缺血再灌注损伤后血脑屏障的影响，并探讨其作用机制。方法将72只SD大鼠随机分为假手术组、对照组、胸腺素β4组各24只。采用线栓法制作大鼠大脑中动脉闭塞局灶性脑缺血再灌注模型，再灌注24 h后，采用干湿重法测定缺血脑组织含水量，通过检测伊文蓝渗透到缺血侧脑组织的含量观察血脑屏障的通透性，应用RT-PCR法检测缺血脑组织紧密连接蛋白5（ Claudin-5）和基质金属蛋白酶-9（MMP-9） mRNA表达。结果脑缺血再灌注损伤24 h后，与假手术组比较，对照组缺血侧脑含水量、伊文蓝含量、MMP-9 mRNA表达明显增加，Claudin-5 mRNA表达显著减少（ P均＜0．01）；与对照组比较，胸腺素β4组缺血侧脑组织含水量、缺血侧伊文蓝含量、MMP-9 mRNA明显降低，Claudin-5 mRNA表达明显升高（P均＜0．01）。结论胸腺素β4对大鼠脑缺血再灌注损伤后的血脑屏障具有保护作用，其作用机制可能是通过促进Claudin-5 mRNA表达和抑制MMP-9 mRNA表达实现的。