【摘要】 目的:探究加兰他敏(GAL)对大鼠脑缺血再灌注后免疫反应和神经再生的影响。方法:SD大鼠随机分为5组(n=30):健康对照组,假手术组,I/R模型组,I/R加低剂量GAL组,I/R加高剂量GAL组。采用改良线栓法建立I/R大鼠模型。HE检测病理组织变化。免疫组化检测神经丝蛋白200(NF-200)的表达。Western blot检测NF-200、生长相关蛋白43(GAP-43)、排斥导向分子(RGMa)的表达水平。ELISA检测血清中肿瘤坏死因子-α(TNF-α)、IL-1β、IL-6、IL-18的含量。Western blot检测核因子E2相关因子2(Nrf2)、血红素氧合酶1(HO-1)、还原型辅酶氧化还原酶1(NQ01)的表达。试剂盒检测脑组织活性氧(ROS)的含量。结果:I/R模型组与假手术组相比,大鼠CA1区出现明显缺血病变; NF-200密度下降,NF-200蛋白表达显著下调,GAP-43蛋白表达显著下调,RGMa表达显著上调;血清中TNF-α、IL-1β、IL-6、IL-18的含量显著上升; Nrf2、HO-1、NQO-1的表达显著下调; ROS的含量显著上升。GAL加药组与I/R模型组相比,大鼠CA1区缺血病变明显改善; NF-200密度上升,NF-200蛋白表达显著上调,GAP-43蛋白表达显著上调,RGMa表达显著下调;血清中TNF-α、IL-1β、IL-6、IL-18的含量显著降低; Nrf2、HO-1、NQO-1的表达显著上调; ROS的含量显著降低。结论:GAL激活Nfr2/ROS细胞信号通路,缓解大鼠脑缺血再灌注后免疫应激反应,诱导神经再生相关蛋白的表达。更多还原

【Abstract】 Objective: To investigate the effects of galanthamine( GAL) on immune response and nerve regeneration after cerebral ischemia reperfusion in rats. Methods: The SD rats were randomly divided into five groups( n = 30) : Healthy control; Sham operation group,I/R model group,I/R plus low dose GAL group,I/R plus High dose GAL group. The model of I/R rat model was established by using the modified plug method. HE staining was used to detect pathological tissue changes. Immunohistochemical was used to detect the expression of NF-200. The expression levels of NF-200,GAP-43 and RGMa were detected by Western blot. The concentration of TNF-α,IL-1β,IL-6 and IL-18 in serum were detected by ELISA Kits. The expression of Nrf2,HO-1 and NQO-1 was detected by Western blot. The content of ROS in brain tissue was detected by related kit. Results: Compared with the sham operation group,there were obvious ischemic lesions in CA1 area of I/R model rats. The NF-200 density decreased,the expression of NF-200 protein was significantly reduced,the expression of GAP-43 protein was significantly reduced,and the expression of RGMa was significantly increased. The concentration of TNF-α,IL-1β,IL-6,IL-18 were increased significantly. The expression of Nrf2,HO-1 and NQO-1 was significantly down-regulated. The content of ROS had increased significantly. Compared with the I/R model group,the ischemic lesions in CA1 area of rats in I/R plus GAL group were significantly improved. NF-200 density increased,the protein expression of NF-200 and GAP-43 was significantly increased,and the expression of RGMa was significantly down-regulated. The concentration of TNF-α,IL-1β,IL-6,IL-18 were decreased significantly. The expression of Nrf2,HO-1 and NQO-1 was significantly up-regulated. The concentration of ROS was significantly reduced. Conclusion: GAL activated Nfr2 and ROS cell signaling pathway to relieve the immune stress response after cerebral ischemia reperfusion in rats and induce the expression of nerve regeneration related proteins.更多还原