摘要
目的观察给予外源性环腺苷酸类似物——双丁酸环腺苷酸(db-cAMP)对脑缺血再灌注(I/R)大鼠轴突再生、患肢运动功能恢复、RhoA信号通路活动的影响,探讨其临床应用可能性及机制。方法将大鼠分为正常组、假手术组、脑I/R对照组、脑室注射生理盐水组(生理盐水组)和脑室注射db-cAMP组(db-cAMP组),采用线栓法制作大鼠大脑中动脉I/R模型,脑室灌注在造模前完成。用逆转录聚合酶链反应(RT-PCR)方法检测缺血灶周边脑组织生长相关蛋白-43(GAP-43)mRNA和RhoAmRNA的表达,用ZeaLonga评分法对患肢运动功能进行评分。结果脑I/R对照组大鼠缺血灶周边脑组织GAP-43mRNA的表达在造模术后6h略有降低,第24小时开始增高,第7天达到高峰,第14天开始降低但仍高于假手术组(P<0.05,P<0.01)。脑I/R对照组大鼠缺血灶周边脑组织RhoAmRNA表达于造模术后6h开始增高,第48小时达到高峰,之后开始下降,第7天和14天仍高于假手术组(P<0.01)。db-cAMP组大鼠缺血灶周边组织GAP-43mRNA在造模术后各时间点均高于脑I/R对照组和生理盐水组大鼠,第7天最显著(P<0.05,P<0.01)。db-cAMP组大鼠缺血灶周边组织RhoAmRNA在造模术后各时间点均显著低于脑I/R对照组和生理盐水组大鼠(P<0.05,P<0.01)。脑I/R对照组,生理盐水组和db-cAMP组大鼠在造模术后各时间点神经功能缺损评分呈相同变化趋势,db-cAMP组大鼠在造模术后第14天神经功能缺损评分显著低于脑I/R对照组和生理盐水组(P<0.05)。结论db-cAMP能够促进脑I/R损伤轴突再生和运动功能的恢复,其机制与抑制RhoA信号通路活动有关。
Objective To observe the effects of db-cAMP on axon regeneration,motor function recovery and RhoA signal pathway in brain of ischemia-reperfusion（I/R）rats to explore its clinical application possibility and mechanism.MethodsThe middle cerebral artery I/R model（MCAIR）was established by nylon monofilament occlusion method in rats.105 rats were randomly assigned into normal group,sham group,I/R control group,intra-cerebraoventricular injection of normal saline（NS）NS group（NS group）and intra-cerebraoventricular injection of db-cAMP group（db-cAMP group）.The expressions of growth associated protein-43（GAP-43）and RhoA mRNA were determined by RT-PCR,and the behavioral scores of wounded limb were measured by Longa standard.ResultsThe expression of GAP-43 mRNA in I/R control group decreased a little at 6 h,began to increase at 24 h,increased significantly and reached the maximum at 7 d after MCAIR,and decreased but still was higher than that of sham group at 14 d（P〈0.05,P〈0.01）.The expression of RhoA mRNA in I/R control group began to increase at 6 h,increased significantly and reached the maximum at 48 h after MCAIR,then decreased but still was higher than that of sham group at 7 and 14 d（P〈0.01）.The expression of GAP-43 mRNA in db-cAMP group was higher than that of I/R control and NS group at any time points,and especially at 7 d（P〈0.05,P〈0.01）.The expression RhoA mRNA in db-cAMP group was much lower than that of I/R control and NS group at any time points（P〈0.05,P〈0.01）.The neurological deficit scores of I/R control,NS and db-cAMP groups at any time points had the same variation tendency,and the score of db-cAMP group was much lower than that of I/R control and NS group at 14 d after MCAIR（P〈0.05）.Conclusionsdb-cAMP can promote axon regeneration and motor function recovery of brain in I/R rats,which is relative to inhibiting RhoA signal pathway.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2009年第7期805-808,共4页
Chinese Journal of Gerontology
基金
重庆市科委自然科学基金(2004-54-83)
