SP600125对蛛网膜下腔出血大鼠海马区神经细胞自噬及神经细胞丢失的影响

发布时间：2018-03-26 08:06

  本文选题：蛛网膜下腔出血　切入点：LC-Ⅱ　出处：《医学研究生学报》2017年05期

【摘要】：目的适度自噬有利于提高神经细胞的存活率;而自噬过度又会引起细胞的调亡。文中旨在探讨SP600125对蛛网膜下腔出血(SAH)大鼠海马区神经细胞自噬及神经细胞丢失的影响。方法将健康雄性清洁级SD大鼠40只按随机化数字表法分为假手术组、模型组、二甲基亚砜(DMSO组)、SP600125组,每组10只。模型组、DMSO组和SP600125组应用血管内穿刺法制成大鼠SAH模型。采用3-0缝合线引入到右颈外动脉,通过颈内动脉推进刺破大脑前动脉和大脑中动脉分叉处,建SAH模型。假手术组除不刺破血管,其余操作均与模型组一致。SP600125组于造模前30 min,利用脑立体定位仪行侧脑室注射3μg/μL SP600125溶液10μL。假手术组和模型组均注射等体积等渗盐水,DMSO组注射等量的DMSO。24 h处死,HE染色观察各组海马区神经元形态及数量;免疫组化染色及Western blot法对p-JNK蛋白以及自噬标志物Beclin-1和LC3-Ⅱ进行定性定量检测。结果 HE结果显示,与假手术组比较,模型组海马区神经元排列紊乱、细胞多呈多边形、数量明显减少;与模型组比较,SP600125组海马区神经元损伤程度有所减轻、细胞明显增多。与假手术组大鼠海马区Beclin-1、LC3-Ⅱ、p-JNK蛋白平均光密度值(1.56±0.28、1.60±0.30、1.58±0.32)比较,模型组(14.66±4.40、12.62±3.46、12.82±3.68)、DMSO组(13.85±3.85、11.59±4.52、13.03±3.53)和SP600125组(9.86±3.14、6.78±2.56、5.60±2.42)明显升高(P0.05);SP600125组较模型组明显降低(P0.05)。与假手术组大鼠海马区Beclin-1、LC3-Ⅱ、p-JNK蛋白表达(0.136±0.014、0.126±0.012、0.102±0.009)比较,模型组(0.474±0.122、0.668±0.130、0.496±0.124)、DMSO组(0.432±0.102、0.628±0.113、0.416±0.094)和SP600125组(0.264±0.106、0.332±0.113、0.219±0.104)明显升高(P0.05);而SP600125组较模型组明显降低(P0.05)。结论SP600125对SAH后神经元细胞具有保护作用,其机制可能与SP600125通过抑制JNK信号通路的活性使自噬适度激活有关。
[Abstract]:Objective moderate autophagy can improve the survival rate of nerve cells. The effect of SP600125 on neuronal autophagy and neuronal loss in hippocampal area of rats with subarachnoid hemorrhage was studied. The computerized digital table was divided into sham-operation group, Model group, dimethylsulfoxide DMSO group (DMSO group), SP600125 group (n = 10), model group (n = 10), DMSO group (n = 10) and SP600125 group (n = 10) were used to establish rat SAH model by intravascular puncture, and 3-0 suture line was applied to the right external carotid artery. The SAH model was established by propulsive puncture of the anterior cerebral artery and the middle cerebral artery by the internal carotid artery. The rest of the operations were consistent with those of the model group. SP600125 group was injected with 3 渭 g / 渭 L SP600125 solution 30 minutes before the model. The sham operation group and the model group were injected with the same amount of DMSO.24 h and HE staining. The morphology and number of hippocampal neurons in each group were observed. Immunohistochemical staining and Western blot method were used to detect p-JNK protein, autophagy markers Beclin-1 and LC3- 鈪，

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