米诺环素抑制脑缺血再灌注后小胶质细胞激活的机制研究

发布时间：2019-04-24 04:48

【摘要】：目的观察米诺环素对大鼠脑缺血再灌注(ischemia/reperfusion,I/R)损伤后小胶质细胞的激活及神经炎症的影响,探讨腺苷A_(2A)受体(adenosine A_(2A)receptor,A_(2A)R)在米诺环素调节小胶质细胞活化中的作用机制。方法采用线栓法阻塞大脑中动脉制作大鼠I/R损伤模型,将30只SD大鼠随机分为假手术组、I/R模型组及米诺环素组〔I/R造模时,米诺环素按体质量3mg/kg(质量浓度为100g/1mL)尾静脉注射,每日2次〕。再灌注24h后,处死大鼠,取大鼠缺血侧脑组织,采用小胶质细胞特异性标记抗体CD11b/c染色、抗A_(2A)R抗体免疫荧光以及双标染色检测缺血灶周围活化的小胶质细胞和A_(2A)R蛋白的表达。Western blot法检测缺血脑组织内白介素-1β、-6(IL-1β、IL-6)及A_(2A)R蛋白的表达。结果 I/R模型组CD11b阳性的小胶质细胞数明显多于假手术组;与I/R模型组相比,米诺环素组IL-1β、IL-6及A_(2A)R蛋白表达下降(P0.05),活化的小胶质细胞数目明显减少。结论米诺环素可抑制局灶性脑I/R损伤所致的小胶质细胞激活及神经炎症反应,其机制可能与下调A_(2A)R蛋白的表达有关。
[Abstract]:Objective to observe the effect of minocycline on the activation of microglia and neuroinflammation after cerebral ischemia-reperfusion (ischemia/reperfusion,I/R) injury in rats, and to explore the effect of adenosine A _ (2A) receptor (adenosine A _ (2A) receptor,) on the activation of microglia and neuroinflammation in rats. The mechanism of A _ (2A) R) in the regulation of microglia activation by minocycline. Methods 30 SD rats were randomly divided into three groups: sham operation group, I R model group and Minocyclovir group. Minocycline was injected into tail vein by body mass 3mg/kg (100g/1mL) twice a day. After 24 hours of reperfusion, the rats were killed and the ischemic brain tissue was taken from the rats. The microglia specific labeled antibody CD11b/c was used to stain. The expression of activated microglia and A2A R protein around ischemic foci were detected by immunofluorescence and double labeling staining. Western blot was used to detect the expression of IL-1 尾, IL-1 尾, IL-6 in ischemic brain tissue. Expression of IL-6 and A2A R protein. Results the number of CD11b positive microglia in the model group was significantly higher than that in the sham operation group. Compared with the model group, the expression of IL-1 尾, IL-6 and A2A R protein in minocyclic group decreased (P0.05), and the number of activated microglia decreased significantly. Conclusion Minocycline can inhibit the activation of microglia and neuroinflammatory response induced by focal cerebral I R injury, which may be related to the down-regulation of A2A R protein expression.
【作者单位】：西南医科大学附属医院神经内科;
【基金】：四川省教育厅科研项目(No.15ZA0168) 泸州市科技计划项目(No.2014S4506) 西南医科大学附属医院课题(No.2015-PT-010)资助
【分类号】：R743.3

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