肝硬化大鼠内脏血管一氧化氮合酶基因表达及活性的动静脉差异  

Differences of nitric oxide synthase expression and activity between splanchnic arterial and venous vessels of cirrhotic rats

作　　者：余金生[1] 梁扩寰[1] 田德安[1] 王天才[2] 唐望先[2] 张文英[2] 刘梅[1] 

机构地区：[1]同济医科大学附属同济医院消化内科,武汉430030 [2]同济医科大学肝病研究所,武汉430030

出　　处：《中华肝脏病杂志》2001年第6期352-355,共4页Chinese Journal of Hepatology

基　　金：国家自然科学基金(39670384)

摘　　要：目的 观察肝硬化内脏血管一氧化氮台酶（ＮＯＳ）表达及活性的动静脉差异在门静脉高压形成机制中的意义。方法 以四氯化碳皮下注射制备大鼠门静脉高压模型，应用免疫组织化学、化学发光以及ＲＴ－ＰＣＲ分别检测大鼠门静脉（ＰＶ）和肠系膜动脉（ＭＡ）组织ＮＯＳ的分布、活性及基因表达。结果　肝硬化组大鼠ＰＶ和ＭＡ血管各层均有ｉＮＯＳ分布，而ｅＮＯＳ则局限于内皮层。肝硬化大鼠内脏血管ＮＯＳ活性［ｐｍｏｌ·ｍｉｎ^(－１)·ｍｇ^(－１)·蛋白（ＰＶ ２３．８２±２．４８，ＭＡ ４３．４６±４．９３）］ 及ｍＲＮＡ表达均较对照组（ＰＶ １６．４８±１．５４，ＭＡ １６．９５±２．３４）显著升高（Ｐ＜０．０５与０．０１）；同时肝硬化大鼠ＭＡ的总ＮＯＳ活性和ｅＮＯＳ活性及ｅＮＯＳ ｍＲＮＡ表达均显著高于ＰＶ（Ｐ＜０．０１）。结论 内脏血管ｅＮＯＳ亚型活性及表达增加可能在肝硬化时ＮＯ产生增多中起主要作用，而ＮＯＳ活性及表达在ＭＡ与ＰＶ之间的动静脉差异，可能是ＮＯ参与门脉高压形成的重要机制之一．Objective To understand the implication of differences of nitric oxide synthase（NOS) expression and activity between splanchnic arterial and venous vessels in the pathogenesis of portal hypertension. Methods Cirrhosis was induced in 100 Wistar rats by subcutaneously administration of carbon tetrachloride. NOS localization, activity and gene expression in the mesenteric artery and the portal vein vessels of both cirrhatic and normal rats were investigated by immunohistochemistry, chemoluminescence and reverse transcription-polymerase chain reaction, respectively. Results There was inducible NOS enzyme isoform in all layers of splanchnic vessels of cirrhotic rats, whereas endothelial NOS isoform largely in vascular endothelia. NOS activity and its mRNA expression all were significantly increased in cirrhotic rats when compared with normal rats（P<0.05 or 0.01).Moreover, the activities of general and constitutive NOS and the ex-pression of endothelial NOS mRNA in cirrhotic rats were significantly higher in the mesenteric artery than in the portal vein（P>0.01). Conclusions Enhanced expression and activity of endothelial NOS enzyme isoform may be mainly responsible for increased NO production of splanchnic vessels in cirrhotic rats, and the differences of NOS expression and activity be-tween the mesenteric artery and the portal vein vessels may be one of the pathogeneses of portal hypertension in which NO might be involved.

关 键 词：肝硬化 内脏血管 一氧化氮合酶 门静脉高压症 大鼠 病理 

分 类 号：R575.2[医药卫生—消化系统]