阿托伐他汀对实验性大鼠脑出血后神经功能保护的研究

Study on Neurological Function Protection of Atorvastatin After Experimental Cerebral Hemorrhage in Rats

目的通过动物实验分析阿托伐他汀对脑出血SD大鼠的神经功能、出血灶组织形态学、脑组织含水量(brain tissue water content,BWC)、水通道蛋白4(aquaporin-4,AQP-4)的治疗效果。方法选取120只SD大鼠,雌雄各半,体重250~300 g,麻醉后向颅内注射自体血构建脑出血SD大鼠模型,剔除死亡大鼠,从存活大鼠中以脑出血动物行为学分级结果选择脑出血分级1~3级SD大鼠,根据性别分层随机抽样选择80只造模成功SD大鼠(雌雄各半),并随机分为治疗组和对照组,每组40只,治疗组给予10 mg/kg阿托伐他汀进行灌胃治疗,对照组注射等量无菌生理盐水,两组以给药前24 h、给药后96 h作为观察点分配SD大鼠,在上述观察点评价两组SD大鼠的神经功能缺损程度,取脑组织称量BWC、在显微镜下观察两组大鼠出血灶状况、并应用免疫组化法做HE染色测定AQP-4的表达水平,并对两组大鼠的上述实验指标进行比较。结果(1)Masao Shmi izu-Sasamata神经行为评分:给药前24 h,两组比较差异无统计学意义(P>0.05);给药后96 h,治疗组显著低于对照组(P<0.05);(2)BWC:给药后96 h,与给药前相比,治疗组BWC减低值多于对照组,差异有统计学意义(P<0.05);(3)光学显微镜下,给药前,两组大鼠脑组织可见红细胞聚集、明显水肿伴随炎性浸润,出血灶面积、最大径差异无统计学意义(P>0.05),给药后96 h,治疗组出血灶面积、炎症浸润均明显减少,而对照组则较给药前无显著变化;(4)给药后96 h,治疗组大鼠脑组织切片中的AQP-4阳性表达值也显著低于对照组(P<0.05)。结论将阿托伐他汀应用于实验性大鼠的脑出血模型的治疗中对于大鼠神经缺损情况、脑水肿、出血灶面积和AQP-4的表达均具有明显的改善作用,值得进一步进行临床试验研究。

Objective To analyze the effect of Atto vastatin on nerve function,histomorphology,water content(brain tissue water content,BWC)and aquaporin 4(aquaporin-4,AQP-4)of cerebral hemorrhage SD rats.Methods Select 120 SD rats,male and female half,weight 250~300 g,anesthesia to intracranial injection of autologous blood after cerebral hemorrhage SD rats model was constructed,eliminate dead rats,from live rats with cerebral hemorrhage in animal behavior classification result choose class 1~3 SD rat brain hemorrhage,according to the gender stratified random sampling to select 80 building successful SD rats(male and female half),and randomly divided into treatment group and control group,each group 40,treatment group given 10 mg/kg atorvastatin lavage treatment,control group injected amount of sterile saline solution,Two groups to give medicine before 24 h,96 h after the treatment as the observation point distribution of SD rats,two groups of SD rats in the above observation point evaluation of nerve function defect degree,take the brain weigh the BWC,two groups of rats is looked at under a microscope hemorrhage stove condition,and using immunohistochemical method to do HE staining to determine the expression level AQP-4,and the experimental index of two groups of rats were compared.Results(1)Masao Shmi Izu-Sasamata neurobehavioral score:24 h before administration,there was no statistically significant difference between the two groups(P>0.05);96 h after administration,the treatment group was significantly lower than the control group(P<0.05);(2)BWC:96 h after administration,compared with before administration,the decrease of BWC in the treatment group was more than that in the control group,with statistical significance(P<0.05);(3)optical microscope,before the treatment,the visible red blood cell aggregation,two groups of rats had obvious edema associated with inflammatory infiltration,hemorrhage stove area,is the largest diameter difference has no statistical significance(P>0.05),96 h after the treatment,bleeding focal area,inflammatory infiltration treatment group were decreased significantly,while the control group was no significant change in drug delivery before;(4)96 h after administration,the positive expression of AQP-4 in brain tissue sections of rats in the treatment group was also significantly lower than that in the control group(P<0.05).Conclusion The application of atorvastadine in the treatment of experimental cerebral hemorrhage model in rats has an obvious effect on the improvement of nerve defect,brain edema,bleeding area and the expression of AQP-4,which is worthy of further clinical study.