脑复合剂对创伤性脑损伤模型大鼠脑内NO、nNOS活性及表达的影响  

Effects of compound decotion on activity and expression of nitric oxide and neuronal nitric oxide synthase in the brain of traumatic brain injury rat model

作　　者：苗静琨[1] 陈启雄 吴小玫[1] 刘振球[1] 张晓萍[1] 

机构地区：[1]重庆医科大学附属儿童医院新生儿科儿童发育疾病研究省部共建教育部重点实验室儿科学重庆市重点实验室重庆市儿童发育重大疾病诊治与预防国际科技合作基地,重庆400014

出　　处：《中国临床药理学与治疗学》2011年第12期1340-1346,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：重庆市卫生局中医药科研资助项目(渝中医20024270)

摘　　要：目的:探讨脑复合剂治疗对创伤性脑损伤(traumatic brain injury,TBI)模型大鼠脑保护作用可能的分子机制。方法:用自由落体打击(Feeney法)建立TBI模型,分别设立假手术组、TBI模型组及中药治疗组。中药治疗组给予脑复合剂10g.kg-1.d-1,假手术组及TBI模型组给予同等剂量的等渗盐水,2次/d,连续7d。分别于TBI后24h、72h、1周等3个时相处死大鼠,用HE染色法观察大脑皮层的形态学变化,化学法检测NO、一氧化氮合酶(NOS)含量、神经元型NOS(nNOS)活性,免疫组化检测nNOS蛋白表达,原位杂交检测nNOS-mRNA表达。结果:TBI模型组各时相大鼠脑内NO、NOS含量、nNOS活性及表达、nNOS-mRNA表达均有不同程度增高,于TBI后24h增高最为明显,持续至1周仍高于假手术组。而中药治疗组各时相大鼠脑组织NO、NOS含量、nNOS活性及表达、nNOS-mRNA表达均明显低于TBI模型组(P<0.05),并于伤后1周接近正常水平。结论:脑复合剂对TBI的保护作用可能与抑制TBI后nNOS-mRNA表达,降低脑组织nNOS活性,从而抑制NO的异常增高,减轻NO介导的神经细胞毒性有关。To explore the possible mechanism of the neuroprotective effect of compound decotion on traumatic brain injury model. METHODS： The traumatic brain injury rat model was induced by improved Feeneys fall weight method and divided into sham operation group, TBI model group and compound decotion treatment group, compound decotion treatment group rats were intragastrically administered with compound decotion at 10 g kg^-1d^-1. Sham operation group and TBI model group were treated with same dose of normal saline, twice per day for seven days. The brains were taken out at 24, 72 h and one week after injury, respectively. The morphological changes were observed by HE staining in the cerebral cortex. The NO and NOS concentration and neuronal nitric oxide synthase （nNOS） activity were detected by neurochemistry stain method, nNOS expression were detected method, nNOSmRNA by in situ hybridization. by immunohistochemical expression were detected RESULTS ： In TBI model group, the concentration of NO and NOS and the activity and expression of nNOS and the expression of nNOSmRNA were markedly elevated at different degrees at different time point and especially 24 hours after injury and still higher than those of sham operation group one week after injury. However, compared with the TBI model group, the concentration of NO and NOS and the activity and expression of nNOS and the expression of nNOSmRNA in compound decotion treatment group were obviously decreased and reach normal level one week after injury （P d0.05）. CONCLUSION： NO and nNOS play an important role in the pathophysiological process of TBI. Inhibition of activated NO and nNOS and mitigate secondary brain injury may represent a potential neuroprotective mechanism for the treatment of TBI with compound decotion.

关 键 词：创伤性脑损伤 一氧化氮 神经元型一氧 化氮合酶 

分 类 号：R965.2[医药卫生—药理学]