机构地区:[1]荆楚理工学院医学院生理教研室,荆门448000 [2]上海交通大学基础医学院解剖与生理学系,上海200240
出 处:《上海交通大学学报(医学版)》2020年第2期180-187,共8页Journal of Shanghai Jiao tong University:Medical Science
基 金:国家自然科学基金面上项目(31571180)。
摘 要:目的·探讨白藜芦醇(resveratrol,Res)对小鼠结肠运动的作用及其机制。方法·采用多通道生理记录仪记录Res(10、20、40和80μmol/L)对小鼠离体结肠平滑肌自发性收缩和结肠移行性复合运动(colonic migrating motor complex,CMMC)的作用。分别用以下工具药对结肠平滑肌肌条预处理:L型Ca^2+通道激活剂BayK8644、非选择性K+通道阻滞剂四乙基氯化铵(tetraethylammonium,TEA)、Na^+通道阻滞剂河豚毒素(tetrodotoxin,TTX)、胆碱能神经元抑制剂阿托品、一氧化氮(NO)合酶抑制剂Nω-硝基-L-精氨酸甲酯(Nco-nitro-L-arginine methyl ester,L-NAME)、ANO1(anoctamin 1)通道抑制剂5-硝基-2-(3-苯基丙基氨基)苯甲酸[5-nitro-2-(3-phenylpropylamino)benzoic acid,NPPB]和SK3通道(small conductance Ca^2+-activated K^+ channel 3)抑制剂apamin。通过洗脱,记录和对比在预处理前后Res对结肠平滑肌肌条自发性收缩的作用。在新鲜分离的结肠平滑肌细胞上,应用全细胞膜片钳技术记录Res对结肠平滑肌细胞的L型Ca^2+通道电流的影响。结果·Res剂量依赖性地显著抑制小鼠离体结肠平滑肌自发性收缩以及结肠近端和远端CMMC。BayK8644可显著阻断Res的抑制作用。Res可显著抑制结肠平滑肌细胞的L型Ca^2+通道电流。TEA不能阻断Res的抑制作用。此外,TTX、阿托品、L-NAME、NPPB和apamin均不影响Res对结肠平滑肌自发性收缩的抑制作用。结论·Res对小鼠结肠运动有抑制作用,其机制可能与抑制小鼠结肠平滑肌细胞L型Ca^2+通道有关,而与各种K+通道、肠神经系统、NO及间质细胞无关。Objective·To investigate the effect of resveratrol(Res)on colonic movement in mice and its mechanism.Methods·The effects of Res(10,20,40,and 80μmol/L)on spontaneous contraction of colonic smooth muscle in mice and colonic migrating motor complex(CMMC)were recorded by using a multi-channel physiological recorder.Colonic smooth muscle strips were pretreated with the following tool medicines:BayK8644(an activator of L-type Ca^2+channel),TEA(tetraethylammonium,a non-selective K+channel blocker),TTX(tetrodotoxin,a Na^+channel blocker),atropine(a cholinergic neuron inhibitor),L-NAME[Nω-nitro-L-arginine methyl ester,a nitric oxide(NO)synthase inhibitor],NPPB[5-nitro-2-(3-phenylpropylamino)benzoic acid,an ANOl(anoctamin 1)channel inhibitor]and apamin[a small conductance Ca^2+-activated K^+ channel 3(SK3)channel inhibitor].By elution,the effects of Res on spontaneous contraction of colonic smooth muscle strips before and after pretreatment were recorded and compared.Finally,the effect of Res on L-type Ca^2+channel currents were recorded by using the whole-cell patch clamp technique in freshly dispersed colonic smooth muscle cells.Results·Res significantly inhibited colonic smooth muscle spontaneous contraction in a dose-dependent manner and markedly decreased CMMC in the proximal and the distal colon.BayK8644 significantly blocked the Res-induced inhibition.Besides,Res dramatically inhibited L-type Ca^2+channel currents in colonic smooth muscle cells.However,TEA did not block the inhibitory effect of Res.In addition,TTX,atropine,L-NAME,NPPB and apamin had no effect on the inhibitory effect of Res on spontaneous contraction of colonic smooth muscle.Conclusion·Res inhibits colonic movement via inhibiting L-type Ca^2+channel in mice,and its mechanism may be irrelevant to potassium channel,the enteric nervous sy stem,NO and interstitial cell.
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