上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (6): 689-.

• 论著（基础研究） • 上一篇    下一篇

山莨菪碱治疗冠状动脉微循环障碍的实验观察

陈 良1, 蒋锦琪1, 张道良1, 杨顺芳2   

  1. 上海交通大学 胸科医院 1.急诊科, 2.核医学科, 上海 200030
  • 出版日期:2010-06-25 发布日期:2010-06-28
  • 作者简介:陈 良（1977—）, 男, 主治医师, 硕士；电子信箱: chliang125chunyan@sina.com。

Experimental observation on treatment of coronary microcirculatory disturbance by anisodamine

CHEN Liang1, JIANG Jin-qi1, ZHANG Dao-liang1, YANG Shun-fang2   

  1. 1.Department of Emergency, 2.Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China
  • Online:2010-06-25 Published:2010-06-28

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摘要：

目的 通过建立新西兰大白兔冠状动脉微血栓模型，观察山莨菪碱对冠状动脉微循环障碍的治疗效果并探讨其作用机制。方法 新西兰大白兔24只，随机分为对照组、模型组和治疗组，每组8只。开胸后阻断升主动脉10 s，模型组经主动脉根部注入月桂酸钠1.5 mg/kg(40 mg/mL) 建立冠状动脉微血栓模型;治疗组于注射月桂酸钠后即刻肌肉注射山莨菪碱10 mg;对照组不予任何处理。模型组和治疗组于术前和术后3 h经耳动脉采血2 mL（对照组随机时间点采血，相隔3 h），测定各组血清中一氧化氮（NO）、内皮素-1（ET-1）、血管内皮生长因子（VEGF）和肌钙蛋白Ⅰ（cTnⅠ）水平。血液样本采集完成后处死所有动物，取心脏制作病理切片，HE染色观察各组微血栓的形成情况并计算微血栓形成率。结果 模型组注射月桂酸钠后3 h，血清NO浓度较术前降低，而ET-1、VEGF和cTnⅠ质量浓度均较术前升高；治疗组各项指标变化趋势与模型组一致，但程度较轻；两组间各指标手术前后差值比较，差异均有统计学意义（P<0.01）。冠状动脉内注入月桂酸钠后3 h，治疗组NO/ET-1比值高于模型组（P<0.05）。各组冠状动脉大动脉中均无血栓形成。对照组微动脉中无血栓形成；模型组和治疗组微动脉中均可见血栓形成，治疗组微血栓形成率低于模型组（P<0.05）。结论 山莨菪碱能有效改善冠状动脉微循环。其机制可能与扩张微血管、减轻内皮受损程度、纠正NO/ET-1的失平衡状态而减少月桂酸钠诱发的血栓形成有关。

关键词: 山莨菪碱, 月桂酸钠, 冠状动脉, 微循环, 微血栓

Abstract:

Objective To observe the therapeutic effects and explore the mechanism of anisodamine on coronary microcirculatory disturbance by establishing coronary microthrombosis models in New Zealand white rabbits. Methods A total of 24 New Zealand white rabbits were randomly divided into control group, model group and treatment group, with 8 rabbits in each group. In model group, coronary microthrombosis models were established by injection of sodium laurate into aortic root at the dose of 1.5 mg/kg (40 mg/mL) with aortic clamping for 10 s. In treatment group, 10 mg of anisodamine was administered by intramuscular injection after injection of sodium laurate. In control group, no treatment was performed. Then, 2 mL blood samples were obtained from ear artery before operation and 3 h after operation in model group and treatment group, while the blood samples in control group were obtained at randomized time points with the interval of 3 h. The serum concentrations of nitric oxide (NO), endothelin-1(ET-1), vascular endothelial growth factor (VEGF) and cardiac troponinⅠ (cTnⅠ) were measured. Animals were sacrificed, pathological sections of heart were prepared, the formation of microthrombus was observed, and the rates of microthrombus formation  were calculated. Results Three hours after injection of sodium laurate in model group, the serum concentration of NO was lower than that before operation, and the concentrations of ET-1, VEGF and cTn I were higher. However, the tendency of changes of NO, ET-1, VEGF and cTnⅠ in treatment group was in line with model group, and  were more moderate. There were significant differences between treatment group and model group in the changes of each parameter before operation and after operation (P<0.01). Three hours after injection of sodium laurate, NO/ET-1 ratio of treatment group was significantly higher than that of model group (P<0.05). There were no thromboses in coronary arteries in each group and no thromboses in arterioles in control group, while there were typical thromboses in arterioles in model group and treatment group. The rate of microthrombus formation in treatment group was lower than that in model group (P<0.05). Conclusion Anisodamine can effectively improve microcirculations, reduce the damage of endothelial cells, correct the imbalance of NO/ET-1, thereby reduce microthrombus induced by sodium laurate, and ultimately, effectively remedy coronary microcirculatory disturbance.

Key words: anisodamine, sodium laurate, coronary artery, microcirculation, microthrombus