Lu Jian-Sheng, Liu Jing-Xia, Zhang Wei-Yu, Liang Sheng-Wang, Wang Dong, Fang Jian
Geriatrics Department of Henan College of Traditional Chinese Medicine, Zhengzhou 450003, China.
Zhongguo Zhong Yao Za Zhi. 2005 Dec;30(24):1939-43.
To assess emodin antagonism to cerebral ischemia injury, and to discuss the mechanism of emodin inhibiting the inflammatory cascade reaction from the levels and expressions of cytokines.
Rats were divided into sham-operated group, model group, Ligustrazine group and emodin groups (low, middle, high dosage). After focal cerebral ischemic model of cerebral middle artery occlusion was duplicated with nylon thread, we took the speciments after ischemia 6 hours, observed the changes of the evaluating score of neural symptoms, brain water ratio and cerebral infarction area, determined the levels of TNF-alpha, IL-beta and TGF-beta in rats brain tissue by radioimmunoassay, detected the expressions of TNF-alpha and VCAM-1 by immunohistochemistry, and measured VCAM-1-mRNA expression by in-situ hybridization.
Compared with sham-operated group, the evaluating score of neural symptoms, brain water ratio and cerebral infarction area of rats in model group were higher (P < 0.01) , the levels of TNF-alpha and IL-1beta of rats brain tissue in model group increased, while the level of TGF-beta was lower, and the expressions of TNF-alpha and VCAM-1 increased (P < 0.01). The evaluating score of neural symptoms, brain water ratio and cerebral infarction area improved obviously in every emodin group, especially in emodin low dosage group. Levels of TNF-alpha, IL-1beta and the expressions of TNF-alpha and ICAM-1 in emodin low dosage group and Ligustrazine group were lower, while the level of TGF-beta was higher. Compared with Ligustrazine group, the changes aboved are more significant in emodin low dosage group (P < 0.01).
The increase of inflammatory cascade reaction mediated by various cytokines such as TNF, IL-1beta, ICAM-1 and the decrease of TGF protection are the important mechanism of cerebral ischemia injury. The mechanism of emodin antagonism to cerebral ischemia injury may be implemented by inhibiting inflammatory cascade reaction and increasing the brain protective factors, such as TGF.
评估大黄素对脑缺血损伤的拮抗作用，并从细胞因子水平及表达探讨大黄素抑制炎症级联反应的机制。
将大鼠分为假手术组、模型组、川芎嗪组及大黄素组（低、中、高剂量）。采用尼龙线复制大脑中动脉闭塞局灶性脑缺血模型后，缺血6小时取材，观察神经症状评分、脑水含量及脑梗死面积变化，用放射免疫法测定大鼠脑组织肿瘤坏死因子-α（TNF-α）、白细胞介素-β（IL-β）和转化生长因子-β（TGF-β）水平，免疫组化法检测TNF-α和血管细胞黏附分子-1（VCAM-1）表达，原位杂交法检测VCAM-1 mRNA表达。
与假手术组比较，模型组大鼠神经症状评分、脑水含量及脑梗死面积升高（P<0.01），脑组织TNF-α、IL-1β水平升高，TGF-β水平降低，TNF-α和VCAM-1表达增加（P<0.01）。各大黄素组神经症状评分、脑水含量及脑梗死面积明显改善，尤以大黄素低剂量组为著。大黄素低剂量组和川芎嗪组TNF-α、IL-1β水平及TNF-α和细胞间黏附分子-1（ICAM-1）表达降低，TGF-β水平升高。与川芎嗪组比较，大黄素低剂量组上述变化更显著（P<0.01）。
TNF、IL-1β、ICAM-1等多种细胞因子介导的炎症级联反应增强及TGF保护作用降低是脑缺血损伤的重要机制。大黄素拮抗脑缺血损伤的机制可能是通过抑制炎症级联反应及增加TGF等脑保护因子实现的。
