二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)对大鼠离体胸主动脉环的舒张作用及机制  

Relaxant effects and mechanisms on vascular tone of dibutyldi-(4-chlorobenzohydroxamato) tin (Ⅳ) (DBDCT) in rat isolated thoracic aorta rings

作　　者：杨彩红[1] 张轩萍[1] 吴博威[2] 李青山[3] 

机构地区：[1]山西医科大学药理学教研室,山西太原030001 [2]山西医科大学生理学教研室,山西太原030001 [3]山西医科大学药学院,山西太原030001

出　　处：《中国药理学通报》2012年第5期620-625,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973603);国家"重大新药创制"科技重大专项资助项目(No 2009ZX09103-104);山西医科大学博士启动基金资助项目(No 03201102)

摘　　要：目的观察抗肿瘤化合物二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)对去甲肾上腺素和氯化钾预收缩健康成年大鼠胸主动脉环的舒张作用,并探讨其作用机制。方法应用离体血管环技术观察DBDCT对大鼠胸主动脉环张力的作用,然后使用一氧化氮合酶(eNOS)抑制剂L-NAME、环氧合酶抑制剂吲哚美辛(Indo)和不同的钾通道阻滞剂预孵后观察DBDCT对血管环张力改变的影响,并观察DBDCT对NE诱发的内钙释放和CaCl2引起的外钙内流的影响。结果 DBDCT对去甲肾上腺素(NE,10-6mol·L-1)或氯化钾(KCl,60 mmol·L-1)预收缩的内皮完整和去内皮大鼠离体胸主动脉环均产生明显的舒张作用,与溶剂组相比差异有统计学意义(P<0.01);但DBDCT对内皮完整与去内皮胸主动脉环作用差异无统计学意义。预先用L-NAME、Indo、KV通道阻断剂四氨基吡啶(4-AP)、KATP通道阻断剂格列苯脲(Gli)孵浴后,DBDCT对NE和KCl预收缩的血管张力的改变与无阻断药时比较,均差异无统计学意义(P>0.05);预先用KCa通道阻断剂四乙胺(TEA)、Kir通道阻断剂氯化钡(BaCl2)孵浴后,DBDCT的舒张血管作用减弱,与无阻断药比较差异有统计学意义(P<0.05);且DBDCT对NE诱发的内钙释放和外钙内流引起的收缩均有明显的抑制作用。结论 DBDCT可明显降低由NE和KCl诱发的血管环张力的升高,且其作用与内皮生成的NO和PGI2均无关,而可能是直接作用于血管平滑肌,激活KCa和Kir通道,抑制钙内流和肌浆网钙释放。Aim To observe the relaxant effects of dibutyldi-（4-chlorobenzohydroxamato） tin（Ⅳ）（DBDCT）,an antitumor compound with high activity on vascular tone in rat isolated aortic rings and the possible mechanism（s）.Methods Isotonic tension of thoracic aortic rings pre-contracted by norepinephrine（NE,10-6 mol·L-1） or KCl（60 mmol·L-1） was recorded.The relaxant effects of DBDCT in 5×10-6 mol·L-1,and effects of various drugs include endothelial nitric oxide synthase（eNOS） inhibitor N G-nitro-L-arginine methyl ester（L-NAME,10-4 mol·L-1）,cyclooxygenase inhibitor indomethacin（Indo,10-5 mol·L-1）,K Ca channel blocker tetraethylammonium（TEA,10-2 mol·L-1）,K V channel blockers 4aminopyridine（4-AP,10-3 mol·L-1）,K ATP channel blocker glibenclamide（Gli,10-5 mol·L-1）,barium chloride（BaCl 2,10-3 mol·L-1） were observed on thoracic aorta rings.Results DBDCT attenuated the contraction induced by NE（10-6 mol·L-1） or KCl（60 mmol·L-1） in rat isolated thoracic aorta rings with intact or denuded endothelium.There were significant differences in the results compared with vehicle group（P0.01）,but not in that between the rings with intact and denuded endothelium at the same concentrations of DBDCT（P0.05）.The relaxant effects of DBDCT showed no significant differences with or without the presence of L-NAME,Indo,Gli,or 4AP,respectively（P0.05）.The relaxant effects of DBDCT on vascular rings were significantly attenuated when pretreated with TEA or BaCl 2（P0.05）.DBDCT significantly inhibited the contraction induced by NE in Ca 2 ＋-free PSS,and the contraction induced by adding CaCl 2.Conclusions DBDCT attenuates the contraction induced by NE or KCl in intact endothelium and denuded endothelium of isolated thoracic aorta.The relaxation of thoracic aortic rings by DBDCT is independent of endothelium,but may be a direct action on vascular smooth muscle.It implicates the activation of K ir and K Ca currents and the inhibition of calcium influx and sarcoplasmic retic

关 键 词：抗肿瘤化合物 二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT) 大鼠 离体胸主动脉环 血管张力 钾通道 

分 类 号：R-332[医药卫生] R311.32