维生素C对肝硬化门静脉高压症患者肠系膜微动脉收缩反应性的影响及其机制

吴婷婷，陈炜， 吴志勇.维生素C对肝硬化门静脉高压症患者肠系膜微动脉收缩反应性的影响及其机制[J].中华普通外科杂志.2013, 28(3):215-218

高血压,门静脉; 肠系膜动脉; 抗坏血酸; 丙二醛

吴婷婷，陈炜， 吴志勇，秦骏，刘德军

200127,上海交通大学医学院附属仁济医院普外科

2013

215-218

万方

目的 研究乙型肝炎后肝硬化门静脉高压症(portal hypertension,PHT)患者的肠系膜微动脉经大剂量维生素C处理后对去甲肾上腺素收缩反应性的变化,探讨维生素C改善PHT内脏血管低反应的机制.方法 取2010年1月至2011年6月在上海仁济医院手术治疗的患者,其中非PHT组6例,PHT组11例,将后者随机分为维生素C治疗组和安慰剂治疗组.在入院后和麻醉诱导开始前抽血测定血浆丙二醛(malonaldehyde,MDA)浓度,术中测定门静脉压力,取空肠旁第三级肠系膜血管及其系膜,利用血管灌流系统测定肠系膜微动脉对去甲肾上腺素的反应,用Western blot方法测定RhoA/ROCK通路中相关蛋白量的表达以及活性的改变.结果 肝硬化PHT患者血浆MDA值远高于非PHT患者,经维生素C治疗后肝硬化PHT患者血浆MDA值明显降低；与非PHT患者相比较,肝硬化PHT患者的离体肠系膜微动脉对去甲肾上腺素剂量反应曲线右移,EC50增大,经维生素C治疗后上述表现逆转；3组患者肠系膜动脉RhoA蛋白量均无明显变化,但是肝硬化PHT患者的ROCK-1蛋白量和活性明显降低,经维生素C治疗后ROCK-1蛋白量和活性显著升高.结论 肝硬化PHT患者处于氧化应激状态,大剂量维生素C治疗能降低PHT患者氧化应激水平,改善了PHT患者肠系膜微动脉对去甲肾上腺素收缩的低反应性,其机制与提高了RhoA/ROCK通路中ROCK蛋白量和活性有关. ： Objective To study the changes of mesenteric arterioles on the contractile response to norepinephrine in patients with cirrhosis and portal hypertension (PHT) caused by hepatitis B after treatment by high-dose vitamin C.Methods Eleven PHT patients and 6 non-PHT volunteer were those undergoing their respective surgeriesat in our hospital from January 2010 to June 2011.The PHT patients were randomly assigned to vitamin C treatment group and placebo treatment group.After admission and before induction of anesthesia,blood taken to mesure plasma concentration of malonaldehyde (MDA).Intraoperative portal pressure was measured.We took the third level intestinal mesentery vessels with their mesentery next to the jejunum and studied the contractile response to norepinephrine of the intestinal mesenteric arterioles.We also measured RhoA/ROCK pathway associated proteins' expression and activity changes by Western-blot method.Results The average value of the plasma MDA of PHT patients with cirrhosis was much higher than that of non-PHT patients.After treatment by vitamin C,the value decreased.The dose-response curve of isolated mesenteric arterioles to norepinephrine from PHT patients with cirrhosis shifted to the right,and the EC50 value was higher than that of non-PHT patients.But this phenomenon was reversed after the patients treated with vitamin C.The protein expression of RhoA in mesenteric arteries did not change significantly among the three groups.But the protein expression and activity of ROCK-1 was significantly reduced in PHT patients with cirrhosis.After treatment with vitamin C,the expression and activity of ROCK-1 in mesenteric arteries of cirrhosis was significantly increased.Conclusion The PHT patients with cirrhosis are in the situation of oxidative stress.The high-dose vitamin C treatment can reduce oxidative stress level and improve contractile hyporeactivity of mesenteric arterioles of PHT patients with cirrhosis to norepinephrine.The protein expression and activity increasement of ROCK in RhoA/ ROCK pathway is involved in thisphenomenon.