论文部分内容阅读
目的观察钩藤碱(rhynchophylline,Rhy)对离体大鼠逼尿肌的作用并探讨其作用机制。方法采用逼尿肌体外张力实验法检测Rhy对大鼠逼尿肌L-型钙通道(ICa-L)及大电导钙离子激活钾离子通道(BKCa)作用。以维拉帕米为对照观察膀胱逼尿肌肌条的收缩及对乙酰胆碱(ACh)依赖细胞内、外钙所致肌条收缩程度的拮抗作用。结果 Rhy和BKCa激动剂NS1619作用相似,亲和力指数(pD2)分别为4.78±0.17、4.53±0.22;BKCa拮抗剂iberiotoxin能竞争性拮抗Rhy,使Rhy累积量效曲线平行右移,拮抗参数(pA2)为7.27±0.16;当Rhy浓度为1~20μmo.lL-1时,使CaCl2累积量效曲线非平行右移,最大反应降低,呈非竞争性拮抗。结论 Rhy通过离子通道(阻滞ICa-L、激活BKCa)抑制膀胱逼尿肌收缩。低浓度(10μmol.L-1)Rhy仅对细胞内钙引起的肌条收缩有抑制作用,而对细胞外钙所致的肌条收缩无影响;随着浓度的增高,Rhy对细胞内、外钙引起的肌条收缩均有抑制作用,且抑制作用逐渐增加。
Objective To observe the effect of rhhychophylline (Rhy) on detrusor muscle of isolated rat and its mechanism. Methods Detrusor in vitro tension test was used to detect the effect of Rhy on detrusor L-type calcium channels (ICa-L) and large conductance calcium-activated potassium channel (BKCa) in rats. Verapamil was used as a control to observe the contraction of the bladder detrusor muscle strips and the antagonism of acetylcholine (ACh) dependence on intracellular and extracellular calcium-induced contractions of muscle strips. Results The results showed that Rhy and BKCa agonist NS1619 had similar effects and their pD2 values were 4.78 ± 0.17 and 4.53 ± 0.22, respectively. BKCa antagonist iberiotoxin competitively antagonized Rhy, Was 7.27 ± 0.16. When the concentration of Rhy was 1 ~ 20μmo.lL-1, the CaCl2 cumulative dose-response curve shifted non-parallel to the right and the maximal response decreased, showing a non-competitive antagonism. Conclusion Rhy inhibits bladder detrusor contraction through ion channels (block ICa-L, activating BKCa). Low concentration of Rhy (10μmol.L-1) only inhibited intracellular calcium-induced contraction of myoblasts, but had no effect on contractility of myoblasts induced by extracellular calcium. With increasing concentration, Rhy inhibited intracellular and extracellular Calcium-induced contraction of muscle strips have inhibitory effect, and the inhibitory effect gradually increased.