摘要
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 study the effect of a new apoE-mimetic peptide on vasospasm and subarachnoid hemorrhage （SAH） in mice and its mechanism. METHODS： Fifty-five C57BL6/JL mice were randomly assigned to 4 groups： sham （ n = 4）, SAH ＋ saline （n=21）, SAH ＋0.6 mg/kg apoE-1410 （n = 14）, SAH ＋ 1.2 mg/kg apoE-1410 （ n = 16 ）. A 5-0 monofilament nylon suture was introduced into the bifurcation of the right anterior cerebral artery （ACA） and the middle cerebral artery （MCA）, and then to perforate the right ACA in SAH groups. In sham operated mice （ n = 4 ） the suture was advanced only until the bifurcation of ACA and MCA to avoid arterial perforation. In the therapeutic experiment, mice received saline, low dose of apoE peptide or high dose of apoE peptide, respectively. Intravenous injections of drug or saline were given 30 min post-operatively with 12 h intervals for 3 d. Behavioral tests were performed daily on all recovery animals for 72 h by an examiner blinded to group assignment. Cerebral vasculars were fixed by perfusion 72 h after SAH to measure the diameter of MCA. RESULTS： Mice after SAH were very weak. The mortality was about 42%. The mortalities of mice treated with the apoE-mimetic peptide at low dose and high dose were 14.2% and 18.8%, respectively, both lower then that of SAH ＋ saline mice （ P 〈 0.05 ）. The diameter of MCA in sham group [ （ 111.3± 7.4 ） μm ] compared with SAH ＋ saline group [ （55.2 ± 17.8 ） μm] decreased by 59% （ P 〈 0.05 ） ; The diameter of MCA in low dose group [ （91.4 ± 16.4） μm] and high dose group [ （83.5 ± 13.6） μm] had a significant improvement as compared with SAH group （P 〈 0.05 ）. The neuroscores in SAH mice （6.7 ± 1.8 ） decreased compared wiht sham-operated mice （ 21.0 ± 0.0, P 〈 0.05） ; The neuroscores in low dose（ 10.9 ±2.6） and high dose （ 10.6 ±4.8 ） apoE-1410 treated mice were higher than those of SAH mice （6.7 ± 1.8, P 〈0.05 ）. The general movement ability in SAH mice （ 58. 8 ± 25. 7 ） was decreased as compared wiht sham-operated mice （ 272. 2 ± 25.7, P 〈 0.05 ） ; The ability in low dose （95.6 ± 18.5） and high dose （95.5 ± 13.2） apoE- 1410 treaed mice were improved as compared with SAH mice （58.8 ± 20.9, P 〈 0.05 ）. CONCLUSION： Exogenous apoE- derived peptide apoE-1410 can significantly improve function and reduce vasospasm after SAH. The one of mechanisms is related to its anti-inflammation after SAH. The novel apoE-derived peptide intervention shows a novel therapeutic potential for SAH and vaso- spasm.
出处
《第四军医大学学报》
北大核心
2007年第12期1071-1074,共4页
Journal of the Fourth Military Medical University
基金
河北省博士基金(06547008D-5)
