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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。
Objective: To investigate the changes of L-type calcium current (ICa-L) in plasma membrane of rats after depression caused by the change of colonic motility in rats with irritable bowel syndrome (IBS). Methods: SPF adult male SD rats were divided into normal control group (n = 15) and depression model group (depression group, n = 15). The depressive model was prepared by means of solitary and chronic unpredictable stress stimulation. After 28 days, the success of depression model was determined by open field test (OFT) and fluid consumption test (FCT). The incidence of IBS was determined based on clinical manifestations, stool traits and numbers generated. Single colon smooth muscle cells were isolated by enzyme-digestion. Whole-cell patch-clamp technique was used to record changes of ICa-L and current-voltage (I-V) curve in colonic smooth muscle cells. Results: Compared with the control group, the rats in the depression group showed slower weight gain and OFT and FCT values (P <0.01), which suggested that the depression model rats were established successfully. (P <0.01). There was a significant negative correlation between OFT and FCT (r> -0.89, P <0.01), and the incidence of gastrointestinal symptoms was significantly increased (P < 0.01), indicating that depression caused severe IBS disease in rats. Compared with the control group, the peak of ICa-L in the membrane of the colon smooth muscle of the depression group was significantly increased in the voltage clamping mode, and the I-V curve obviously shifted to the bottom and shifted to the left. When the clamping potential was +10 mV, the ICa-L of the colon smooth muscle cells in the depression group increased from (-21.31 ± 4.79) pA to -33.52 ± 4.45 pA in the control group (P <0.01). There was a significant positive correlation between defecation particle number and water content in depressed rats (r> 0.91, P <0.01). Conclusions: Depression can cause obvious IBS in the gastrointestinal tract in rats. The possible mechanism is that depression induces the electrical remodeling of ICa-L in the membrane of rat colonic smooth muscle, which leads to the change of intestinal motility. form.