NOGO⁃A在创伤性脑损伤后大鼠脑组织含量表达及干预实验研究

Experimental research of expression and intervention of NOGO-A in brain tissue of rats after traumatic brain injury

目的研究创伤性脑损伤(TBI)后大鼠脑组织内NOGO-A分子含量及大鼠脑超微结构的改变以及二者与RHOA/ROCK信号传导通道的联系。方法45只健康SD大鼠按照随机数字表法分为对照组、中度创伤组和干预组,每组15只。中度创伤组和干预组大鼠采用击锤、撞杆自由落体原理致伤,制作TBI大鼠模型,干预组大鼠创伤后立即给予静脉注射盐酸法舒地尔注射液。TBI后24 h处死各组大鼠,采用电子显微镜观察各组损伤区脑组织细胞超微结构的变化,采用免疫组化技术观察各组大鼠脑组织中NOGO-A蛋白的含量,并测定NOGO-A蛋白的灰度值。结果TBI后24 h,中度创伤组及干预组大鼠脑组织损伤区出现病理性损伤,干预组程度较中度创伤组轻。3组大鼠脑组织内NOGO-A蛋白表达量比较,差异有统计学意义(F=176.085,P<0.05),中度创伤组的NOGO-A蛋白含量最高,干预组次之,对照组最低。结论TBI后24 h大鼠脑内损伤区出现细胞核、线粒体损害及细胞水肿,NOGO-A含量增加。RHOA/ROCK信号通路被阻断后能够改善TBI大鼠脑组织损伤区细胞超微结构损害以及减少NOGO-A的含量。

Objective To study the changes of the content of the NOGO-A and the ultrastructure in rat brain tissue after traumatic brain injury(TBI),and their relationship with RHOA/ROCK transduction pathway.Methods Forty-five healthy SD rats were randomly divided into control group,moderate trauma group and intervention group,with 15 rats in each group.The TBI rat model was established by hammer and free falling rod in moderate trauma group and intervention group.The rats in the intervention group were given fasudil hydrochloride injection intravenously immediately after trauma.The rats in each group were sacrificed 24 h after TBI.The ultrastructural changes of brain tissue cells in the injured area of each group were observed by electron microscope,the content of NOGO-A protein in brain tissue of each group was observed by immunohistochemical technique,and the gray value of NOGO-A protein was measured.Results Twenty-four hours after TBI,pathological injury occurred in the brain tissue injury area of rats in the moderate trauma group and the intervention group,and the intervention group was less severe than in the moderate trauma group.There was significant difference in the expression of NOGO-A protein in the brain tissue of the three groups(F=176.085,P<0.05).The moderate trauma group had the highest NOGO-A protein content,followed by the intervention group and the lowest in the control group.Conclusion Twenty-four hours after TBI,the injure of cell nucleus、mitochondria and cells edema appeared in the damage area of brains of rats,the distribution and the content of the NOGO-A in the damage area of rats increased.Blocking of the RHO/ROCK signaling pathway can improve the damage of the ultrastructure of the brain cell in the damage area and reduce the content and distribution of NOGO-A.