山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (7): 15-23.doi: 10.6040/j.issn.1671-7554.0.2019.1273
• • 上一篇
龙婷婷,谢明,周璐,朱俊德
LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde
摘要: 目的 探讨侧脑室注射Noggin蛋白对小鼠脑缺血再灌注损伤(CIRI)后学习、记忆能力及齿状回(DG)结构的影响,以期为临床缺血性脑血管疾病的预防与治疗提供新思路。 方法 240只小鼠随机分为:假手术组(n=80)、缺血再灌注损伤组(I/R组,n=80)、缺血再灌注损伤+Noggin治疗组(Noggin组,n=80),每组再分为1、3、7、14 d共 4个亚组;取材前1天采用Y型迷宫检测小鼠学习记忆能力(n=5);然后比色法检测缺血侧脑组织超氧化物歧化酶(SOD)与丙二醛(MDA)含量(n=5);2,3,5-氯化三苯基四氮唑(TTC)染色检测脑梗死面积(n=5); 尼氏染色与免疫荧光检测DG神经元与胶质原纤维酸性蛋白(GFAP)阳性细胞变化(n=5);Western blotting法检测骨形态发生蛋白4(BMP4)蛋白表达(n=5)。 结果 随着损伤时间的增加,I/R组、Noggin组与假手术组相比,小鼠神经功能评分升高(F组别=21.19, P<0.001; F时间=25.13, P<0.001),学习、记忆能力均下降[(F组别=216.10, P<0.001; F时间=260.10, P<0.001)、(F组别=114.40, P<0.001; F时间=184.60, P<0.001)],脑梗死面积增加(F组别=2374, P<0.001; F时间=3 292, P<0.001),SOD活性降低(F组别=1 426, P<0.001; F时间=1 723, P<0.001),MDA含量升高(F组别=2.22, P<0.001; F时间=6.33, P<0.001),神经元数量减少(F组别=148.90, P<0.001; F时间=485.50, P<0.001),GFAP阳性细胞和BMP4蛋白表达量增加[(F组别=40.18, P<0.001; F时间=141.90, P<0.001)、(F组别=426.70, P<0.001; F时间=1 329, P<0.001)]。在各个相同时间点,与I/R组相比,Noggin各组小鼠神经功能评分降低(P<0.001),学习、记忆能力提高(P<0.001),脑梗死面积减小(P<0.001),SOD活性升高及MDA含量降低(P<0.001),神经元数量增加及染色变浅(P<0.001),GFAP阳性细胞和BMP4 蛋白表达量降低(P<0.001)。 结论 Noggin蛋白对小鼠脑缺血再灌注损伤后学习、记忆能力提高与DG组织损伤修复有改善作用,其作用机制可能与阻断BMP4蛋白表达和抑制胶质细胞的反应性增生有关。
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