Rho激酶抑制剂对缺血性脑白质损伤的实验性干预研究

The effect of Rho kinase inhibitor on the ischemic white matter impairment of rats

目的探讨Rho激酶对缺血性脑白质损害的影响及Rho激酶抑制剂对缺血性脑白质损害的干预效果。方法雄性Wistar大鼠60只,随机分为对照组、缺血组和治疗组,每组20只。缺血组和治疗组给予双侧颈总动脉结扎,对照组给予假手术处理;术后治疗组给予法舒地尔腹腔注射,对照组和缺血组给予生理盐水腹腔注射。手术1个月后评价测定各组大鼠脑深部白质纤维密度、星形胶质细胞数目以及Rho激酶mRNA表达水平。结果缺血组大鼠脑深部白质纤维密度较对照组明显降低,星形胶质细胞数目明显增多,Rho激酶mRNA表达水平明显增高,差异有统计学意义(P<0.05);治疗组大鼠脑深部白质纤维密度较缺血组明显增高,星形胶质细胞数目明显减少,差异有统计学意义(P<0.05)。结论 Rho激酶异常活化与缺血性白质损害相关,Rho激酶抑制剂可改善慢性低灌注状态下大鼠脑白质损害。

Objective To determine the role of Rho kinase in the ischemic white matter impairment induced by chronic hypoperfusion and the effect of Rho kinase inhibitor on ischemic white matter impairment. Methods Sixty male Wistar rats were divided into three groups：control group,ischemic group and treatment group. The rats of ischemic group and treatment group received bilateral carotid artery ligation, and the rats of treatment group received daily intraperitoneal injection of fasudil,an inhibitor of Rho kinase. Kluver-Barrera＇s myelin sheath staining,immunohistochemical examination for glial fibrillary acidic protein and reverse transcriptase polymerase chain reaction for Rho kinase were performed on the 30th day after the operation. Results Rats of ischemic group had lower density of white matter fibers,increased number of astrocytes in deep white matter areas and upregulated expression of Rho kinase mRNA as compared with control group. Compared with ischemic group, rats of treatment group had increased white matter fiber density and decreased number of astrocytes in deep white matter areas. Conclusion Abnormally activated Rho kinase may be an important cause of ischemic white matter impairment induced by chronic hypoperfusion. Treatment with Rho kinase inhibitor can attenuate the white matter impairment induced by chronic hypoperfusion.