慢性脑缺血致认知功能障碍大鼠皮层Rho激酶表达变化

ROCK expression in rat with cognitive dysfunction due to chronic cerebral ischemia

目的探讨慢性脑缺血致大鼠认知功能障碍与Rho激酶(ROCK)及作用产物α-平滑肌激动蛋白(SMA)表达变化。方法健康雄性Wistar大鼠54只,随机分为假手术组、模型组和法舒地尔组。各组再根据缺血时间分为3、6、9w三组,每组6只。采用2VO建立慢性脑缺血模型,Morris水迷宫检测学习记忆功能,免疫组化检测ROCK2、α-SMA表达。结果与假手术组相比,模型组和法舒地尔组大鼠逃避潜伏期和游泳路径均明显延长(P<0.05);缺血3w起,缺血组大鼠皮层ROCK2、α-SMA表达明显增高,法舒地尔干预后,大鼠学习记忆成绩不同程度改善,ROCK2、α-SMA表达下降,与模型组相比差异显著(P<0.05)。结论ROCK参与大鼠慢性脑缺血致认知功能障碍,脑组织存在ROCK表达上调与功能活化,ROCK抑制剂法舒地尔能够减轻神经功能损伤从而改善学习记忆功能。

Objective To investigate the expressions of Rho kinase （ROCK） and α-smooth muscle actin （SMA） in the rats with cognitive dysfunction due to chronic cerebral ischemia. Methods 54 healthy male Wistar rats were randomly divided into sham operation, model and fasudil groups, then subdivided into 3 subgroups according the 3, 6, 9 w of ischemia time, 6 rats in each subgroup. Chronic cerebral ischemia animal models were established by 2VO. Learning and memory function were tested by Morris water maze, and ROCK2 and α- SMA expressions were measured by immunohistochemistry. Results The escape latency and swim distance of model and fasudil groups were longer than those of sham operation group（ P 〈 0. 05 ）. Expressions of ROCK2 and α-SMA increased significantly in ischemia group since 3 w of ischemia, with intervention of fasudil, ROCK and α-SMA expression decreased and cognitive function improved significantly, having obvious difference from those of model group （P 〈 0.05 ）. Conclusions Up-regulation and activation ROCK interfere with cognitive dysfunction due to chronic cerebral ischemia, fasudil has protective effect of neuron and can improve learning and memory function.