大黄苷元注射抗大鼠脑缺血损伤炎性级联反应

目的评价大黄苷元抗脑缺血损伤作用,并从细胞因子水平及表达方面探讨其抑制脑缺血炎性级联反应机制。方法将大鼠分为假手术组、模型组、川芎嗪组、大黄苷元组(低、中、高剂量)。线栓法制备大鼠局灶性脑缺血6h模型。观察神经症状积分、脑组织含水量、梗死面积,放射免疫法测定脑组织TNF-α、IL-1β、TGF-β水平,免疫组织化学法测定TNF-α、VCAM-1表达,原位杂交法测定VCAM-1-mRNA表达。结果与假手术组比较,模型组大鼠神经症状积分和脑含水量及梗死面积增加,脑组织TNF-α和IL-1β水平增高(P<0·01)、TGF-β水平降低(P<0·01),TNF-α和VCAM-1的表达增强(P<0·01)。与模型组比较,川芎嗪组和大黄苷元低剂量、中剂量组神经症状积分和脑含水量及梗死面积明显降低,大黄苷元低剂量组较中、高剂量组和川芎嗪组尤为明显。大黄苷元低剂量组和川芎嗪组TNF-α和IL-1β水平及TNF-α、ICAM-1表达明显降低,TGF-β水平增高(P<0·01),大黄苷元低剂量组较川芎嗪组尤为明显。结论由多种细胞因子如TNF-α、IL-1β、ICAM-1介导的炎性级联反应增强和TGF-β的保护作用减弱是脑缺血损伤的重要机制。大黄苷元抗脑缺血损伤作用机制可能是通过抑制缺血脑组织炎性级联反应和提高脑保护因子如TGF-β水平而实现的。

Rhubarb aglycone injection antagonism to inflammatory cascade reaction of rats with cerebral ischemia injury

Aim To assess rhubarb aglycone antagonism to cerebral ischemic injury and discuss the mechanism of rhubarb aglycone inhibiting the inflammatory cascade reaction of cerebral ischemia from the levels and expressions of cytokines. Methods Rats were divided into sham-operated group, model group, Ligustrazine group and rhubarb aglycone groups (low, middle, high dosage). Focal cerebral ischemic model of cerebral middle artery occlusion was duplicated with nylon thread. Taking speciments after ischemia for 6 h. Observing changes of neural symptoms by evaluating score, brain water ratio and cerebral infarction area, determining levels of TNF-α, IL-1β and TGF-β of rats brain tissue by radio-immunity, then determining expressions of TNF-α and VCAM-1 by immunohistochemical, VCAM-1mRNA expression was measured by in-situ hybridization. Results Compared with sham-operated group, the evaluating score of neural symptoms, brain water ratio and cerebral infarction area of model group were higher(P<0.01), levels of TNF-α and IL-1β of rats brain tissue in model group increased,while the level of TGF-β was lower, and expressions of TNF-α and VCAM-1 enhanced(P<0.01). Compared with model group, the evaluating score of neural symptoms, brain water ratio and cerebral infarction area in Ligustrazine and rhubarb aglycone groups (low, middle dosage) decreased significantly, especially in rhubarb aglycone low dosage group. Levels of TNF-α and IL-1β and expressions of TNF-α and VCAM-1 in rhubarb aglycone low dosage group and Ligustrazine group decreased obviously, while the level of TGF-β was higher. Compared with Ligustrazine group, changes above were more significant in rhubarb aglycone low dosage group. Conclusions The increase of inflammatory cascade reaction mediated by various cytokines such as TNF-α,IL-1β,ICAM-1 and the decrease of TGF-β protection were the important mechanism of cerebral ischemia injury. The mechanism of rhubarb aglycone antagonism to cerebral ischemia injury may be implemented by inhibiting inflammatory cascade reaction and increasing the brain protective factors, such as TGF-β.