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梗阻性黄疸大鼠胸主动脉血管平滑肌KATP通道异常激活
KATP channels in ASMCs of Obstructive jaundice rats are excessive activation

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DOI:
作者:
袁亚伟，卢占英，王龙，俞卫锋
Yuan Yawei,Lu Zhanying,Wang Long,Yu Weifeng
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
1、Department of Anesthesiology and Critical Care, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University. 2、The experimental teaching center，The Second Military Medical University. 3、Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University.
关键词:
梗阻性黄疸；KATP通道；血管低反应性
obstructive jaundice ；KATP channels ；hyporesponsiveness
摘要:
目的 探究三磷酸腺苷敏感性钾通道（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SD大鼠，体重180～200g，随机分为：空白对照组（Control组）、假手术组（Sham组）和胆管结扎组（BDL组）。术后连续7天观测各组大鼠体重、尿液、粪便等指标。术后第7天，腹腔注射2%戊巴比妥钠麻醉，开腹确认造模成功后取大鼠胸主动脉。将三组大鼠的胸主动脉分别制备血管环，去掉血管内皮，再施以不同处理分别为：Control+肾上腺素（NE）/硝普钠（SNP）组、Sham+NE/SNP组、BDL+NE/SNP组、Control+格列苯脲（Glibenclamide，Glib）+NE/SNP组、Sham+Glib+NE/SNP组、BDL+Glib+NE/SNP组。①比较Control、Sham和BDL组大鼠胸主动脉血管基础张力值情况。②比较用血管活性药物NE处理后Control、Sham和BDL组大鼠胸主动脉血管收缩反应性的改变情况。③比较用KATP通道阻断剂Glib处理后Control、Sham和BDL组大鼠胸主动脉血管收缩幅度的改变情况（Glib处理后NE诱导的收缩幅值 / 高钾液诱导的最大收缩幅值×100%）。④比较SNP处理后Control、Sham和BDL组血管张力的改变情况。⑤比较用KATP阻断剂Glib处理后Control、Sham和BDL组大鼠胸主动脉血管舒张反应性的变化（KATP阻断剂Glib处理后SNP诱导的血管张力 / 静息状态下血管的基础张力×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。与Control和Sham组大鼠比较，①BDL组大鼠胸主动脉基础张力显著降低（* P＜0.05，n=6）。②BDL组大鼠胸主动脉对NE（10-9、10-8、10-7、10-6mol/L）诱导的最大收缩张力显著降低（* P＜0.05，n=6）。③用KATP阻断剂Glib处理后，BDL组大鼠胸主动脉对NE（10-7、3×10-7、10-6、3×10-6 mol/L）诱导的最大收缩幅度显著增大（* P＜0.05，n=6），且具有剂量依赖性。④BDL组大鼠胸主动脉在SNP（10-9、10-8、10-7、10-6mol/L）处理后舒张幅值显著增大（* P＜0.05，n=6）⑤KATP阻断剂Glib处理后，BDL组大鼠胸主动脉对SNP（10-6、3×10-6 mol/L）介导的舒血管效应反应性显著减小（* P＜0.05，n=6），具有剂量依赖性。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，舒张反应明显。
Objective: To study the impact of ATP-sensitive potassium channels (KATP channels) on contraction and relaxation of thoracic aorta in obstructive jaundiced rat. To further clarify the role of KATP channels in vascular hyporesponsiveness in obstructive jaundice. Methods: 36 male SD rats, weight 180~200g, were randomly divided into three groups: group control (n=12), group sham (n=12), group BDL (n=12). Body weight, urine and feces etc.were detected each day. Seven days after operation, rats those have been undergone laparotomy to confirm the effects of BDL (intraperitoneal injection of 2% sodium pentobarbital for anesthesia) was prepared for thoracic aorta rings without endothelial cells. the thoracic aorta rings was then divided into 6 groups: control+NE or SNP, sham+NE or SNP, BDL+NE or SNP, control+Blib following NE or SNP, sham+Blib following NE or SNP and BDL+Blib following NE or SNP. The outcomes were following: 1) to compare the vasoconstriction among control、sham and BDL groups. 2) to compare the vasoconstriction after NE treatment among control、sham and BDL groups. 3) to compare the vasoconstriction of NE after Glib pretreatment among control、sham and BDL groups, which indicated by the change percentage of vasoconstriction (NE-induced contraction after Glib pretreatment/high potassium-induced contraction*100%). 4) to compare the vasodilation after NE treatment among control、sham and BDL groups. 5) to compare the vasodilation of SNP after Glib pretreatment among control、sham and BDL groups, which indicated by the change percentage of vasodilation (SNP-induced vasodilation after Glib pretreatment/high potassium-induced vasodilation*100%). Results: the liver of BDL rats became diffusely enlarged, yellow color and hard texture, the stump of common bile duct was cystic dilatation. 1) Contraction of thoracic aorta in BDL group was significantly reduced (p<0.05). 2) NE-induced maximal contraction (10-9、10-8、10-7、10-6mol/L) of thoracic aorta in BDL group was significantly lower than that in control and sham groups. 3) There was a significantly larger change percentage of NE-induced contraction after Glib pretreatment in BDL rats compared with that in control and sham rats with dose-dependent properties (P＜0.05). 4) Thoracic aorta in BDL rats had a relatively weaker SNP-induced vasodilation (P＜0.05). 5) A Significantly larger change percentage of SNP-induced vasodilation was observed in BDL rats rather than in control and sham rats (P＜0.05) and also with dose-dependent properties. Conclusion: KATP channels are involved in vasoconstriction and vasodilation of thoracic aorta in obstructive jaundiced rat. over-activation of KATP channels is a potential mechanism of vascular hyporesponsiveness in obstructive jaundice.

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