梗阻性黄疸大鼠胸主动脉血管平滑肌细胞三磷酸腺苷敏感性钾通道异常激活

发布时间：2018-05-31 23:11

本文选题：梗阻性黄疸 + ATP敏感性钾通道　；参考：《上海医学》2015年06期

【摘要】：目的探究ATP敏感性钾通道(KATP通道)在梗阻性黄疸条件下对大鼠胸主动脉收缩和舒张功能的影响,为进一步阐明梗阻性黄疸病理状况下血管平滑肌KATP通道对血管舒缩功能的影响及其机制提供实验依据。方法雄性Sprague-Dawley大鼠,体重180~200g,随机分为正常对照组、假手术组和胆管结扎组(BDL组),术后连续7d观测各组大鼠的体重、尿液、粪便。术后第7天,腹腔注射2%戊巴比妥钠麻醉大鼠,开腹观察肝脏和胆总管的形态变化,确认造模成功后取胸主动脉。将3组大鼠的胸主动脉分别制备血管环,去掉血管内皮,再施以不同处理。比较3组大鼠胸主动脉血管基础收缩力情况。比较用血管活性药物肾上腺素(NE)处理后3组大鼠胸主动脉血管收缩力的改变情况。比较用KATP通道阻断剂格列苯脲(Glib)处理后3组大鼠胸主动脉血管收缩力变化百分比(Glib处理后NE诱导的收缩张力/高钾液诱导的收缩张力×100%)。比较硝普钠(SNP)处理后3组大鼠血管收缩力的改变情况。比较用KATP阻断剂Glib处理后3组大鼠胸主动脉血管收缩力变化百分比(Glib处理后SNP诱导的血管收缩力/静息状态下的血管收缩力×100%)。结果 BDL组大鼠肝脏呈弥漫性肿大、颜色发黄、质地变硬,肝脏胆总管残端呈囊状扩张。BDL组大鼠的胸主动脉基础收缩力值显著低于正常对照组和假手术组(P值均0.05)。NE(1×10-9、1×10-8、1×10-7、1×10-6 mol/L)诱导后BDL组大鼠胸主动脉收缩力均显著低于同剂量NE诱导的正常对照组和假手术组(P值均0.05)。用KATP通道阻断剂Glib处理后,BDL组大鼠胸主动脉对NE(1×10-7、3×10-7、1×10-6、3×10-6 mol/L)诱导的血管收缩力变化百分比显著大于同剂量NE诱导的正常对照组和假手术组(P值均0.05)。经KATP通道阻断剂Glib处理后,BDL组大鼠胸主动脉对SNP(1×10-6、3×10-6 mol/L)诱导的舒血管效应显著弱于同剂量SNP处理的假手术组和正常对照组(P值均0.05),血管收缩力百分比显著大于同剂量SNP诱导的正常对照组和假手术组(P值均0.05)。结论梗阻性黄疸大鼠胸主动脉平滑肌KATP通道存在过度激活,由此导致血管收缩反应被抑制,舒张反应增强。
[Abstract]:Objective to investigate the effects of ATP sensitive potassium channel (K ATP channel) on the systolic and diastolic function of thoracic aorta in rats with obstructive jaundice. To further elucidate the effect of vascular smooth muscle KATP channel on vasomotor function and its mechanism in obstructive jaundice. Methods male Sprague-Dawley rats, weighing 180 ~ 200g, were randomly divided into normal control group, sham operation group and bile duct ligation group. The body weight, urine and feces of each group were observed 7 days after operation. On the 7th day after operation, 2% pentobarbital sodium was injected intraperitoneally to anesthetized rats. The morphologic changes of liver and common bile duct were observed. Vascular rings were prepared from thoracic aorta of three groups of rats, vascular endothelium was removed and treated with different treatments. The basic contractility of thoracic aorta in three groups was compared. The changes of vasoconstrictive force of thoracic aorta in three groups were compared after treatment with epinephrine (NE), a vasoactive drug. The contractility of thoracic aorta in three groups was compared after treatment with KATP channel blocker glibenclamide (Glib). The contractile tension induced by NE / high potassium solution was compared in three groups after glib treatment. The changes of vasoconstrictive force in three groups were compared after SNP-treated with sodium nitroprusside. The percentage of vasoconstriction of thoracic aorta in the three groups after treatment with KATP blocker Glib was compared. The contractility of aorta induced by SNP / resting state was compared. Results the liver of BDL group showed diffuse swelling, yellow color and hard texture. The basal contractility of thoracic aorta in rats with cystic dilatation of hepatic common bile duct stump was significantly lower than that in normal control group and sham-operation group (0.05).NE(1 脳 10-9, 1 脳 10-8, 1 脳 10-7 脳 10-6 mol / L). After induction, the contractility of thoracic aorta in BDL group was significantly lower than that induced by NE at the same dose. P value of normal control group and sham operation group were 0.05. After treated with KATP channel blocker Glib, the percentage of vasoconstriction induced by NE(1 脳 10-7 + 3 脳 10-7 + 1 脳 10-6 mol / L in thoracic aorta of rats was significantly higher than that of normal control group and sham operation group induced by NE at the same dose (P < 0.05). After treated with KATP channel blocker Glib, the vasodilative effect of thoracic aorta of SNP(1 脳 10-6 + 3 脳 10-6 mol / L group was significantly weaker than that of sham-operation group and normal control group treated with the same dose of SNP, and the percentage of vasoconstriction was significantly higher than that of the same dose of SNP. The P values of normal control group and sham operation group induced by SNP were 0.05. Conclusion the KATP channel of thoracic aortic smooth muscle in rats with obstructive jaundice is over-activated, which leads to the inhibition of vasoconstriction and the enhancement of diastolic response.
【作者单位】：第二军医大学附属东方肝胆外科医院麻醉与危重病科;第二军医大学基础医学实验教学中心;上海交通大学医学院附属仁济医院麻醉科;
【基金】：国家自然科学基金面上项目资助(81170427)
【分类号】：R575

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