摘要
目的:研究热休克蛋白90(heat shock protein 90,HSP 90)在门静脉高压症(portal hypertension,PHT)内脏动脉中的表达变化,探讨其在高动力循环形成中的作用及可能的机制。方法:检侧四氯化碳(CCl4)诱导的肝硬化PHT组(n=7)和对照组(n=7)大鼠的门静脉血流速度(portal vein blood flow velocity,PBV)、门静脉直径、门静脉血流量(portal vein blood flow,PBF)和门静脉压力(portal vein pressure,PP),离体肠系膜微动脉对去甲肾上腺素(norepinephrine,NE)的反应性、HSP 90特异性抑制剂格尔德霉素(geldanamycin,GA)对离体肠系膜微动脉收缩反应的影响以及肠系膜动脉内HSP 90和内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)的蛋白表达变化。结果:①PHT组大鼠PBV和PBF明显低于对照组,门静脉直径在PHT组与对照组之间无统计学差异,GA对PHT组PBV及PBF无明显改善;②PHT组大鼠PP明显高于对照组,GA对PHT组PP并无明显降低作用;③PHT组大鼠肠系膜微动脉对NE的收缩反应性明显降低,50%作用浓度明显增大,GA能部分改善这种低反应性;④PHT组大鼠肠系膜动脉内HSP 90和eNOS的蛋白水平较对照组明显上调,GA明显降低PHT组肠系膜动脉HSP 90表达的同时,也降低了eNOS的表达。结论:CCl4诱导肝硬化PHT肠系膜动脉中过度生成的HSP 90可能是通过增加eNOS的表达降低肠系膜动脉对NE的反应性参与内脏高动力循环的形成。
Objective To study the variation of heat shock protein 90 （HSP 90） in the splanchnic arteries in portal hypertension （PHT）, and to explore its effect on the pathogenesis of hyperdynamic circulation. Methods The difference of the parameters was compared between rat model of PHT induced by CCL （PHT group, n=7） and control group （n=7）, including portal vein blood flow velocity（PBV）, portal vein diameter, portal vein blood flow （PBF）, portal vein pressure（PP）, the reaction of isolated mesenterie microcirculation arteries to norepinephrine（NE）, the influence of geldanamycin（GA）, the specific inhibitor of HSP 90 on both the isolated mesenterie mieroeirculation arteries and the expression of HSP 90 and endothelial nitric oxide synthase（eNOS） in mesentery arteries. Results （ 1 ）PB~ and PBF of PHT group rats was apparently lower than that of the control group. However no difference of diameter of portal vein between two groups was observed. GA could not improve PBV and PBF in PHT group. （2）PP was much higher in PHT group than that in the control group. GA did not reduce PP in PHT group. （3）The contractile response of mesenteric microcirculation arteries to NE decreased significantly while ECs0 increased greatly, GA partially promoted such hyporesponsiveness. （4）The protein level of HSP 90 and eNOS in mesentery arteries of PHT group rose significantly than that of the control group. GA significantly down- regulated the protein level of HSP 90 and eNOS simultaneously in mesentery arteries of PHT group. Conclusions The excessive expression of HSP 90 produced in mesentery arteries in PHT induced by CCL may increase the protein level of eNOS. In turn, it decreased mesentery arteries＇ reactivity to NE. Our study suggests that elevation of HSP 90 may participate in the forming process of hyperdynamic circulation.
出处
《外科理论与实践》
2013年第2期131-136,共6页
Journal of Surgery Concepts & Practice
基金
上海市教育委员会科研创新项目(12zz110)
关键词
门静脉高压症
高动力循环
热休克蛋白90
内皮型一氧化氮合酶
Portal hypertension
Hyperdynamic circulation
Heat shock protein 90
Endothelial nitric oxide synthase
