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目的研究咪达唑仑、丙泊酚、依托咪酯和氯胺酮对大鼠离体结肠远端纵形肌肌条收缩活动的影响及其可能的影响机制。方法制备大鼠离体结肠纵形肌肌条,随机分为对照组、非TTX组和TTX组,对照组加入二甲亚砜(DMSO)5μL;非TTX组直接加入不同累积浓度的咪达唑仑、丙泊酚、依托咪酯或氯胺酮;TTX组加入电压门控Na+通道阻滞剂河豚毒(TTX)10μmol/L阻断结肠内神经元动作电位的产生和传导后,再分别加入不同累积浓度的静脉麻醉药,加药方式同非TTX组。以平均肌张力变化为指标,记录三组肌条收缩活动的变化。结果对照组:DMSO对结肠肌条收缩张力无明显影响。非TTX组:咪达唑仑、丙泊酚、依托咪酯和氯胺酮分别在药物累积浓度达到1×10-5、1×10-5、1×10-6和3×10-6mol/L时降低结肠远端纵形肌收缩幅度(P<0.05～0.01),肌条张力降低幅度随药物浓度升高而加大。依托咪酯虽然在低浓度(1×10-6mol/L)时即可降低肌条自主收缩幅度,但当浓度累积至1×10-4mol/L时,与等浓度的咪达唑仑和丙泊酚相比,其降低幅度却较小(P<0.05)。TTX组:用电压门控Na+通道阻滞剂TTX预处理后,咪达唑仑、丙泊酚和依托咪酯仍降低大鼠结肠远端纵形肌肌条收缩张力,且与非TTX组相比,降低幅度明显增大(P<0.05～0.01);而氯胺酮非但不降低肌条收缩张力,反而增高收缩张力。结论咪达唑仑、丙泊酚、依托咪酯和氯胺酮均抑制大鼠结肠远端纵形肌自主收缩,其机制可能与肠道平滑肌细胞收缩和肠神经系统活动有关。
Objective To investigate the effect of midazolam, propofol, etomidate and ketamine on contractile activity of the distal longitudinal muscle strips of the colon of rats and its possible mechanism. Methods The isolated rat longitudinal muscle strips were prepared and randomly divided into control group, non-TTX group and TTX group. DMSO was added to the control group and 5μL of DMSO. Non-TTX group was added with midazolam Propofol, etomidate or ketamine. After TTX treatment, the voltage-gated Na + channel blocker tetrodotoxin (TTX) 10μmol / L blocked the generation and conduction of action potentials in the colon, and then added different accumulation Concentration of intravenous anesthetics, dosing with non-TTX group. With the change of average muscle tension as index, the change of contractile activity of the three groups was recorded. Results The control group: DMSO had no significant effect on the contractile tension of colonic muscle strips. In the non-TTX group, midazolam, propofol, etomidate and ketamine at drug cumulative concentrations of 1 × 10-5, 1 × 10-5, 1 × 10-6, and 3 × 10-6 mol / L, respectively Reduce the contraction of distal colon longitudinal muscle (P <0.05 ~ 0.01), muscle tension decreased with the drug concentration increased. Etomidate decreased the contractile amplitude of myoblasts at low concentration (1 × 10-6mol / L), but when the concentration was 1 × 10-4mol / L, the concentration of midazolam and propofol Propofol, compared to its reduction was smaller (P <0.05). TTX group: Midazolam, propofol and etomidate still reduced the contractile tension of the distal longitudinal muscle strips of rats after TTX preconditioning with voltage-gated Na + channel blocker, and contrasted with non-TTX group (P <0.05 ~ 0.01). However, ketamine not only did not reduce the contractile tension of muscle strips, but increased the contractile tension. Conclusion Midazolam, propofol, etomidate and ketamine both inhibit the autonomic contractility of the distal longitudinal muscle of the colon, which may be related to the contraction of intestinal smooth muscle cells and the activity of enteric nervous system.