神经调节素在脑缺血再灌注损伤中的抗炎作用机制研究

目的研究神经调节素-1β（NRG-1β）对小鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法应用线栓法建立小鼠大脑中动脉闭塞再灌注（MCAO／R）模型，经颈内动脉微量注射NRG．1B（2μg／kg）干预治疗，氯化三苯基四氮唑（TTC）染色观察脑梗死体积，免疫荧光染色检测神经细胞凋亡，免疫组织化学检测酪氨酸激酶受体（ErbB-4）和基质金属蛋白酶-9（MMP-9）的表达。结果脑缺血再灌注损伤后，神经细胞凋亡数量明显增多，并诱导ErbB-4和胶质细胞MMP-9表达增强。应用NRG-1β干预治疗后，缺血脑组织梗死体积和细胞凋亡数量较对照组显著减小，ErbB-4受体表达增强，而胶质细胞MMP-9表达下调（P〈0．05）。结论NRG—1β可能通过下调脑缺血再灌注损伤诱导的胶质细胞MMP-9表达和抑制细胞凋亡，而发挥其抗炎作用。

Anti-inflammatory effect of neuregulin on cerebral ischemic reperfusion injury in rats and its mechanism

Objective To study the inhibitive effects of neuregulin-1β （NRG-1β） on neuronal apoptosis and inflammatory responses after cerebral ischemic reperfusion injury in rats and its mechanism. Methods Middle cerebral artery occlusion reperfusion （MCAOJR） models were established by intraluminal thread methods in rats. Neuregulin-1β （2μg / kg） was injected into the internal carotid artery for treatment. The Cerebral infarction volume was revealed by tetrazolium chloride （TTC） stain, the apoptosis positive cells were counted by immunofluorescence assay, and the expression of tyrosine kinase receptor （ErbB-4） and matrix metalloproteinase- 9 （MMP-9） in gliocytes were determined by immunohistochemical assay. Results The number of neuronal apoptosis cells increased significantly and the expression of ErbB-4 and MMP-9 in gliocytes was highly enhanced after ischemic reperfusion injury. After treated with NRG-1β, the cerebral infarction volume and the number of neuronal apoptotic cells were reduced significantly. ErbB-4 receptors were over-expressed while the MMP-9 was down-regulated （P 〈0.05 ）. Conclusion NRG-1β may play an anti-inflammatory effect by down-regulating the expression of MMP-9 in gliocyte and inhibiting the neuronal apoptosis induced by ischemia reperfusion injury.