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-  2017 

抑郁引起大鼠结肠动力学改变导致肠易激综合征的L-型钙电流的变化 Effect of Abnormal Colon Motility Induced by Depression on Irritable Bowel Syndrome via Altering L-Type Calcium Current in Rat Colonic Myocytes

Keywords: 抑郁,结肠平滑肌细胞,离子通道重构,肠易激综合征,动作电位失常

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Abstract:

目的:探讨抑郁引起大鼠结肠动力学改变导致肠易激综合征(IBS)后细胞膜上L-型钙电流(ICa-L)变化。方法:SPF级成年雄性SD大鼠分为正常对照组(对照组,n=15)和抑郁症模型组(抑郁组,n=15)。抑郁模型制备方法是采用孤养加慢性温和不可预知性应激刺激方式进行,28d后通过旷场试验(OFT)和液体消耗试验(FCT)确定抑郁模型成功。根据临床表现、生成的粪便性状和数量确定IBS发生率。酶解法分离单个结肠平滑肌细胞,全细胞膜片钳技术记录结肠平滑肌细胞膜上ICa-L及其电流-电压(I-V)曲线变化。结果:与对照组比较,抑郁组大鼠出现体重增长减慢,OFT和FCT值显著降低(P均<0.01),提示抑郁大鼠模型建立成功;抑郁组大鼠出现严重体质减弱,排便颗粒数及其含水量明显增高(P均<0.01),与OFT和FCT值比较呈显著的负相关(r值均>-0.89,P均<0.01),胃肠道症状的发生率显著增高(P<0.01),说明抑郁引起大鼠出现严重的IBS病症。在电压钳制方式下,与对照组比较,抑郁组大鼠结肠平滑肌细胞膜上ICa-L峰值显著增大,其I-V曲线明显下移到最底部和向左偏移。当钳制电位为+10mV时,抑郁组大鼠结肠平滑肌细胞ICa-L由对照组的(-21.31±4.79)pA增加为(-33.52±4.45)pA(P<0.01)。与抑郁大鼠的排便颗粒数及其含水量进行比较,具有显著正相关(r均>0.91,P均<0.01)。结论:抑郁能引起大鼠胃肠道出现明显的IBS病症,其发生机制可能是抑郁诱发了大鼠结肠平滑肌细胞膜上ICa-L增加出现电重构,造成结肠性动作电位失常促使肠动力学改变形成

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