姜丽 杨子平 包怡敏

摘要：目的 观察银杏酮酯（GBE50）对急性血瘀证大鼠血流动力学和心肌组织肿瘤坏死因子（TNF）-α通路的影响，探讨其作用机制。方法 采用皮下注射盐酸肾上腺素复合冰水浴法制作大鼠急性血瘀证模型。将雄性SD大鼠随机分为正常组、模型组和GBE50组，灌胃相应药物干预11 d后造模。次日观察各组血流动力学变化，RT-PCR检测心肌组织TNF-α、TNFR1、TNFR2 mRNA表达，放免法检测心肌组织TNF-α蛋白表达，免疫组化检测心肌组织TNFR1和TNFR2蛋白表达。结果 模型组血流动力学指标呈现低于正常组的趋势；与模型组比较，GBE50组左心室收缩峰压平均值、左室发展压明显增大，室内压最大上升速率时间明显减少（P<0.05），GBE50组心肌组织TNF-α、TNFR1、TNFR2蛋白表达明显升高，TNFR2 mRNA表达明显升高（P<0.05）。结论 GBE50能改善急性血瘀证大鼠血流动力学指标，并对心肌组织TNF-α通路具有调控作用，增加保护性受体TNFR2表达可能是其保护心功能的机制之一。

关键词：银杏酮酯；血瘀证；血流动力学；肿瘤坏死因子-α；肿瘤坏死因子受体；大鼠

DOI：10.3969/j.issn.1005-5304.2017.11.009

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）11-0034-05

Abstract： Objective To observe the effects of Ginkgo biloba extract 50 （GBE50） on hemodynamics and myocardial tissue TNF-α pathway in rats with acute blood stasis syndrome； To discuss its mechanism of action. Methods A model of acute blood stasis syndrome was established by subcutaneous injection of epinephrine hydrochloride and ice bath. Male SD rats were divided randomly into normal group， model group and GBE50 group. After medicine was administrated by gavage for 11 days， the acute blood stasis model was established. The hemodynamic changes were observed in the next day. The expressions of TNF-α， TNFR1 and TNFR2 mRNA were detected by RT-PCR. The expressions of TNF-α， TNFR1 and TNFR2 protein were tested by radioimmunoassay and immunohistochemistry. Results The hemodynamics of the model group was lower than that of the normal group. Compared with model group， GBE50 could increase mLVSP， DP and decrease t-dp/dtmax （P<0.05）. The protein expressions of TNF-α， TNFR1， and TNFR2 in GBE50 group were higher than those in model group， and TNFR2 mRNA expression increased significantly in GBE50 group （P<0.05）. Conclusion GBE50 can ameliorate the decline of hemodynamics of rats with acute blood stasis syndrome， and regulate the myocardial TNF-α pathway. Increasing the expression of protective receptor TNFR2 may be one of the mechanisms of protecting cardiac function.

Key words： Ginkgo biloba extract 50； blood stasis syndrome； hemodynamics； TNF-α； TNF receptor； rats

基金項目：国家自然科学基金（81303256）

通讯作者：包怡敏，E-mail：yiminbao@163.com

血瘀证是临床常见证型，与心脑血管疾病、肿瘤发生等密切相关。目前研究认为，血瘀证生物学病理变化多反映在血液流变学方面，包括全血黏度、血浆黏度、血小板聚集性增强，体外血栓形成的干湿量及长度增加，纤维蛋白原增高等[1]，但对血瘀证血流动力学变化报道较少。临床研究表明，血瘀证患者存在过度的炎症反应，且炎症与血瘀证的病理、病机和治疗等方面关系密切[2]。作为血瘀证发展过程中的炎症反应和心功能的桥梁因子，肿瘤坏死因子（TNF）-α在一定程度上决定血瘀证内在病理机制的发展变化与转归[3]；而TNF-α主要通过与细胞表面的2种TNF受体（TNFR1、TNFR2）的结合，发挥其生物学效应[4]。……