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目的:探讨脑心通对大鼠局灶性脑缺血损伤后行为学及脑组织肿瘤坏死因子α表达的影响。方法:实验于2004-03/11在河北医科大学第二医院神经内科实验室进行。取成年健康雄性SD大鼠150只,制造大鼠局灶性大脑中动脉阻断造模手术后,将大鼠随机分为5组,即脑心通4g/kg组、2g/kg组、1g/kg组、生理盐水和假手术组,各组又分为6,24,48,72h,7d5个亚组,每亚组均为6只大鼠。脑心通各剂量组均为灌胃给药,生理盐水组给同体积的生理盐水,于相应时间点进行行为学评分后处死动物快速取脑,观察脑含水量的变化,病理切片苏木精-伊红染色观察组织病理学改变,免疫组织化学的方法测定肿瘤坏死因子α的动态变化。结果:实验中有8只大鼠死亡,后随机补充,进入结果分析仍为150只大鼠。①行为学评分:大鼠在大脑中动脉阻断后手术对侧肢体存在不同程度瘫痪,在术后48和72h时神经功能缺损最为明显,7d时神经功能基本恢复正常。②病理观察:除假手术组外,其余各组在脑梗死后6h局部可见少量散在炎性细胞浸润;梗死后48h,炎性细胞浸润明显增多;并持续到7d。③脑组织含水量:与假手术组相比,其他各组在各时间段均增加。术后24,48h脑心通4g/kg组为(78.95±1.36)%,(79.44±1.01)%,脑心通2g/kg组为(79.03±0.87)%,(80.46±1.54)%,低于同期的脑心通1g/kg组和生理盐水组[(79.21±0.68)%,(82.02±1.76)%,(79.30±1.11)%,(82.68±0.91)%,P<0.05]。④肿瘤坏死因子α阳性细胞表达:与假手术组相比,其他各组在各时间段均增加,梗死后6h开始增多,48h达高峰。术后24,48h脑心通4g/kg组为(27.6±2.1),(18.4±1.5)个,脑心通2g/kg组为(38.4±2.1),(23.2±3.3)个,低于同期的脑心通1g/kg组和生理盐水组[(50.4±5.6),(30.8±5.3),(52.8±3.7),(33.0±4.7)个,P<0.05]。结论:脑心通可能通过减轻脑水肿,降低脑内肿瘤坏死因子α的表达减少炎性细胞的浸润,从而对大鼠缺血脑组织损伤产生保护作用。
Objective: To investigate the effect of Naoxintong on behavior and the expression of tumor necrosis factor-α in brain tissue after focal cerebral ischemic injury in rats. METHODS: The experiment was performed at the Department of Neurology, Second Hospital of Hebei Medical University from March to November 2004. 150 adult healthy male Sprague-Dawley rats were used to make focal cerebral artery occlusion and the rats were randomly divided into 5 groups: Naoxintong 4g/kg group, 2g/kg group, 1g In the group of kg/kg, saline, and the sham group, each group was divided into 6, 24, 48, 72, and 7 days, and 5 subgroups. Each subgroup was 6 rats. Each group of Naoxintong was intragastrically administered, and physiological saline was given to the same volume of normal saline. At the corresponding time point, behavioral scores were performed and the animals were sacrificed to quickly take the brain to observe the changes of brain water content. Histopathic slices of hematoxylin Eosin staining was used to observe the histopathological changes. Immunohistochemistry was used to determine the dynamic changes of tumor necrosis factor alpha. Results: Eight rats died during the experiment and were randomly supplemented. The results of the analysis were still 150 rats. 1Behavioral scores: Rats had different degrees of paralysis of the contralateral limbs after middle cerebral artery occlusion. Neurological deficits were most obvious at 48 and 72 hours after surgery. The neurological function returned to normal at 7 days. 2 pathological observation: In addition to the sham group, other groups showed a small amount of diffuse inflammatory cell infiltration at 6 h after cerebral infarction; 48 h after infarction, inflammatory cell infiltration increased significantly; and continued until 7d. 3 Brain tissue water content: Compared with the sham group, other groups increased at each time period. At 24 and 48 hours after operation, the brain and heart 4g/kg group was (78.95±1.36)%, (79.44±1.01)%, and the brain and heart 2g/kg group was (79.03±0.87)%, (80.46±1.54)%, low. At the same time, the Naoxintong 1g/kg group and the saline group [(79.21±0.68)%, (82.02±1.76)%, (79.30±1.11)%, (82.68±0.91)%, P<0.05]. 4 Tumor necrosis factor α positive cells: Compared with the sham group, other groups increased at each time period, began to increase at 6 h after infarction, and peaked at 48 h. At 24 and 48 hours after operation, the brain and heart 4g/kg group was (27.6±2.1), (18.4±1.5), and the brain and heart 2g/kg group was (38.4±2.1), (23.2±3.3), lower than the same period. Brain Naoxin 1g/kg group and saline group [(50.4±5.6), (30.8±5.3), (52.8±3.7), (33.0±4.7), P<0.05]. Conclusion: Naoxintong can reduce cerebral edema and reduce the expression of tumor necrosis factor alpha in brain. It can reduce the infiltration of inflammatory cells and protect the brain tissue of rats from ischemic injury.