丹参素对异丙肾上腺素损伤大鼠内皮血管活性的保护作用及机制研究  

Protection of Danshensu on endothelial vascular functions in rats damaged by isoproterenol and its mechanism

作　　者：汪旻晖[1,2] 单娇娇 李浣钧[1] 丁小英[1] 李宏仁[1] 刘淳[1] 张立[1] 汤依群[1] 

机构地区：[1]中国药科大学临床药学教研室,江苏南京210009 [2]皖南医学院弋矶山医院安徽省药物临床评价中心,安徽芜湖241001

出　　处：《中草药》2013年第1期59-64,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(30772609);国家级大学生实践创新训练计划项目(J0630858)

摘　　要：目的观察异丙肾上腺素持续给药对大鼠内皮血管活性的影响及丹参素的保护作用。方法雄性SD大鼠随机分为5组:对照组,模型组,丹参素高、低剂量(3、10 mg/kg)组,缬沙坦(10 mg/kg)阳性对照组。血管切片染色观察组织形态改变;观察各组大鼠内皮完整胸主动脉环对内皮依赖型血管收缩剂杨梅黄酮、内皮依赖型血管舒张剂乙酰胆碱的反应性,观察缝隙连接开放剂AAP-10和阻断剂18α-甘草次酸对模型大鼠血管环舒缩功能的影响;Western blotting法测定血管缝隙连接蛋白Connexin 43(Cx43)、Connexin 40(Cx40)的表达水平。结果模型组大鼠血管中膜厚度明显增加,收缩舒张功能均下降;与模型组相比,丹参素给药组大鼠血管组织结构有所改善,血管舒缩功能显著提高(P<0.05)。与模型组相比,模型大鼠胸主动脉环用18α-甘草次酸孵育后收缩功能显著降低(P<0.05),用AAP-10孵育后收缩功能恢复,舒张功能改变不明显。Western blotting结果显示,丹参素和缬沙坦治疗组均可有效逆转异丙肾上腺素引起的Cx40、Cx43水平降低(P<0.05)。结论丹参素可有效保护异丙肾上腺素引起的大鼠血管环收缩与舒张功能损伤,其机制可能与丹参素保护血管上缝隙连接蛋白表达,逆转受损信号传导有关。Objective To investigate the protective effect ofDanshensu （DSS） on the endothelial vascular functions of rats damaged by sustained delivery of isoproterenol （ISO）. Methods Normal male SD rats were randomly divided into control, model, DSS low （3 mg/kg）, DSS high （10 mg/kg） groups, and Valsartan （Val, 10 mg/kg） as positive control group. Vascular slice staining was used to observe morphology changes. The tension and relaxation of endothelial intact aorta tings by endothelium-dependent vascular inotropic agent myricetin and vasodilator acetylcholine （Ach） in rats of each group were observed. The effects of gap junction opener AAP-10 and blocker 18a-glycyrrhetic acid on systolic and diastolic function of rat vascular rings were observed. The expression of Connexin43 （Cx43） and Connexin40 （Cx40） was detected using Western blotting. Results The thickness of vascular was significantly increased in the model group, and the tension and relaxation functions were both decreased. Compared with the model group, the structure of vascular tissue in rats treated with DSS was improved, the tension and relaxation functions were obviously improved （P 〈 0.05）; The tension and relaxation functions of rat thoracic aortic rings were obviously decreased after treated with 18α-glycyrrhetic acid （P 〈 0.05）, and the tension function was restored but the relaxation function showed no obvious change after treated with AAP-10. Western blotting results showed that DSS and Val groups could effectively reverse the decrease of Cx43 and Cx40 induced by ISO （P 〈 0.05）. Conclusion DSS could effectively prevent and improve the aortic vascular function in rats sufferedfrom the vascular damage induced by ISO. The mechanism may be related with DDS protection on the expression of vascular connexin and retroconversion of damaged signal transduction.

关 键 词：丹参素 异丙肾上腺素 内皮血管 缝隙连接蛋白 信号传导 

分 类 号：R282.710.5[医药卫生—中药学] R972[医药卫生—中医学]