CAJ | 학술논문

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.
목적 연구을형간염후간경화문정맥고압증(portal hypertension,PHT)환자적장계막미동맥경대제량유생소C처리후대거갑신상선소수축반응성적변화,탐토유생소C개선PHT내장혈관저반응적궤제.방법 취2010년1월지2011년6월재상해인제의원수술치료적환자,기중비PHT조6례,PHT조11례,장후자수궤분위유생소C치료조화안위제치료조.재입원후화마취유도개시전추혈측정혈장병이철(malonaldehyde,MDA)농도,술중측정문정맥압력,취공장방제삼급장계막혈관급기계막,이용혈관관류계통측정장계막미동맥대거갑신상선소적반응,용Western blot방법측정RhoA/ROCK통로중상관단백량적표체이급활성적개변.결과 간경화PHT환자혈장MDA치원고우비PHT환자,경유생소C치료후간경화PHT환자혈장MDA치명현강저；여비PHT환자상비교,간경화PHT환자적리체장계막미동맥대거갑신상선소제량반응곡선우이,EC50증대,경유생소C치료후상술표현역전；3조환자장계막동맥RhoA단백량균무명현변화,단시간경화PHT환자적ROCK-1단백량화활성명현강저,경유생소C치료후ROCK-1단백량화활성현저승고.결론 간경화PHT환자처우양화응격상태,대제량유생소C치료능강저PHT환자양화응격수평,개선료PHT환자장계막미동맥대거갑신상선소수축적저반응성,기궤제여제고료RhoA/ROCK통로중ROCK단백량화활성유관.
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.