【作者】 胡跃强；

【导师】 胡国恒；

【作者基本信息】 湖南中医学院 ， 中医内科学， 2003， 硕士

【摘要】 目的：探讨以清热活血法为主要组方原则的清热活血方对急性脑缺血大鼠海马及大脑皮质IL-1β、ICAM-1、PMNL、EAA、脑组织含水量的影响及对梗死区病理形态学脑损害的预保护性作用。方法：采用随机分组对照实验，以在老龄及高脂血症基础上结扎双侧颈总动脉造成大鼠持续性脑缺血模型，各组大鼠于造模后3h、6h、12h、24h四个时间点分别用ELISA法及免疫组化法等方法检测海马区及大脑皮质的IL-1β、ICAM-1、PMNL、EAA的含量及脑组织含水量，光镜下观察海马不同分区组织病理形态学改变，并对海马CA1区神经元丢失做定量计数。结果：①大鼠脑缺血3h后，海马区IL-1β开始上升，24h达高峰；而其顶叶皮质ICAM-1表达及白细胞浸润6h后开始上升，24h后继续增加，较IL-1β明显滞后。②清热活血方可显著减轻脑组织IL-1β、ICAM-1、PMNL的含量，与模型组及川芎嗪对照组比较均有显著性差异（P<0.05），该方并可显著降低缺血脑组织兴奋性氨基酸的含量。③药物干预组大鼠海马区以神经元变性为主，轻度神经元坏死、丢失及胶质增生；模型组大鼠可见海马区严重神经元坏死、丢失及胶质增生和脑水肿；模型组CA1区锥体细胞计数及额叶皮质含水量与药物干预组、假手术组比较差异有统计学意义（P<0.05），且大剂量中药组优于药物对照组（P<0.05）。 结论：①清热活血方下调IL-1β、ICAM-1的含量，抑制脑内PMNL聚集，降低兴奋性氨基酸的含量及脑组织含水量，从而减轻缺血大鼠脑损伤，可能是该方保护脑梗死后脑损伤的作用机理之一。②IL-1β介导的ICAM-1、PMNL参与脑梗死后脑损伤病理过程。更多还原

【Abstract】 [Objective]: To explore the protective effect of QRHX prescription based on the main principle of Qing Re Huo Xue on cerebral ischemia (CI) injury.[Methods]: The rat models with CI were prepared and randomly devided into normal group, sham—operated group, CI group, treatment group with different dosage of QRHX prescription, and tetramethylpyrazine control group. The changes in the following parameters, including the contents of interleukin—1β(IL—1β), Intercellular adhesive molecule(ICAM—1), Polymorphonuclear leukocyte (PMNL), excitatory amino acid(EAA) and water in brain tissue were observed, with methods of ELISA and immunohistochemistry and HPLC respectively at 3h,6h,12h,24h after operation. Meanwhile, the different pathologic changes were observed by light microscope and the neuron number in the hippocampus CA1 was counted at those points respectively.[Results]: QRHX prescription was able to decrease the contents of IL-1β, ICAM-1, and EAA in brain tissue obviously (P<0.05).The difference was significant as compared with QRHX high dose group and tetramethylpyrazine control group(p<0.05). The neuronal degeneration and lightly neucrosis and glue hyperplasia occurred in hippocampus areas of the rats pretreated by drugs, but the damage was more severe in the model group. The number statistics difference of neuron in CA1 area between the<WP=6>model group，Sham-operated group and drug-pretreated was significant (p<0.05).[Conclusions]: The results suggest an important role for IL-1β、ICAM-1 mediated PMNL adhesion in the evolution of brain injury following CI. Downregulating the expression levels of IL-1β and ICAM-1 protein, and inhibiting the accumulation of PMNL may ascribe to the protective effects of QRHX prescription on inflammatory brain injury following CI.更多还原