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目的:探讨新合成的拟载脂蛋白E(apoE)对蛛网膜下腔出血(SAH)的治疗作用及机制.方法:55只C57BL6/JL小鼠随机分为:假手术组,SAH组,低剂量(SAH+apoE-1410,0.6mg/Kg)组和高剂量(SAH+apoE-1410,1.2mg/Kg)组.显微操作戳破右侧大脑中动脉(MCA)和大脑前动脉(ACA)分叉处造成SAH模型.术后30min开始经尾静脉给药,每12h一次,连用3d.每日检测小鼠的一般精神状态、神经功能评分、综合运动能力评分.术后第3日测量MCA直径.结果:术后SAH组小鼠精神萎靡,食欲下降,有的难进食水,体质量下降,死亡率为42.8%.高、低剂量组与SAH组比较,一般症状明显减轻,死亡率分别为14.2%和18.8%,与SAH组比较,显著降低(P<0.05).MCA直径在假手术组为(111.3±7.4)μm,与SAH组(55.2±17.8)μm比较,平均缩小了59%(P<0.05);低、高剂量组MCA分别为(91.4±16.4)μm和(83.5±13.6)μm,与SAH组(55.2±17.8)μm比较,MCA痉挛程度下降(P<0.05).神经功能评分在SAH组(6.7±1.8)明显低于假手术组(21.0±0.0,P<0.05);高剂量组(10.6±4.8)、低剂量组(10.9±2.6)的神经功能评分分别明显高于单纯SAH组(6.7±1.8,P<0.05);但在两个剂量组间未见差别(P>0.05).综合运动能力评分在SAH组(58.8±25.7)明显低于假手术组(272.2±25.7,P<0.05);高剂量组(95.5±13.2),低剂量组(95.6±18.5)的综合运动能力分别明显高于单纯SAH组(58.8±20.9,P<0.05).结论:外源性拟apoE对SAH及脑血管痉挛有一定的治疗作用,其机制与降低神经系统对损伤的炎性反应有关,拟apoE有可能成为治疗SAH的新措施.
AIM: To investigate the therapeutic effect and mechanism of newly synthesized apolipoprotein E (apoE) on subarachnoid hemorrhage (SAH) .Methods: Fifty-five C57BL6 / JL mice were randomly divided into sham operation group, SAH group, low (SAH + apoE-1410,0.6mg / Kg) group and high dose (SAH + apoE-1410,1.2mg / Kg) group.Microscopy punctured the right middle cerebral artery (MCA) and the anterior cerebral artery (ACA ) Bifurcation SAH model caused by 30min after the start of intravenous administration, once every 12h, once every 3d, daily detection of the general state of mind in mice, neurological score, exercise score .3 day after the measurement MCA diameter.Results: After SAH group, the symptoms of apomorphine and appetite in SAH mice were poor, and the body weight was decreased, the mortality rate was 42.8% .Compared with SAH group, the symptoms of SAH group were significantly reduced, and the mortality rate (14.2% vs 18.8%, respectively) compared with SAH group (P <0.05) .MCA diameter was (111.3 ± 7.4) μm in sham operation group, which was reduced by 59% on average compared with SAH group (55.2 ± 17.8) μm % (P <0.05). The MCA of low and high dose groups were (91.4 ± 16.4) μm and (83.5 ± 13.6) μm, respectively. Compared with SAH group (55.2 ± 17.8) μm, MCA spasm was decreased (P <0.05). Neurological score was significantly higher in the SAH group (6.7 ± 1.8) (21.0 ± 0.0, P <0.05). The scores of neurological function in high dose group (10.6 ± 4.8) and low dose group (10.9 ± 2.6) were significantly higher than those in SAH group (6.7 ± 1.8, P < <0.05), but there was no difference between the two dose groups (P> 0.05), and the score of comprehensive exercise ability in SAH group (58.8 ± 25.7) was significantly lower than that in sham operation group (272.2 ± 25.7, P <0.05) (95.5 ± 13.2) and low dose group (95.6 ± 18.5) were significantly higher than that of the SAH group (58.8 ± 20.9, P <0.05) .Conclusion: Exogenous pseudo-apoE has a significant effect on SAH and cerebral vasospasm A certain therapeutic effect, the mechanism and reduce the nervous system damage to the inflammatory response, the proposed apoE may be a new measure for the treatment of SAH.