一氧化氮合酶在门静脉高压症中表达的实验研究

The Expression of Nitric Oxide Synthase in Portal Hypertensive Rats

比较肝前(PHPH)、肝内型门静脉高压鼠(IHPH)、门腔分流鼠(PCS)以及正常鼠(SO)内脏组织和血管中原生型(cNOS)和诱生型一氧化氮合酶(iNOS)活性及cNOS mRNA和iNOS mRNA的表达。方法:用分光光度法检测大鼠腹主动脉、门静脉、小肠和大肠组织中cNOS和iNOS活性,并用RT-PCR法半定量测定其cNOS mRNA和iNOSmRNA的表达。结果:门静脉高压鼠的动脉中iNOS活性和iNOS mRNA表达均显著地增加,其表达在转录水平受调节。cN03的活性和cNOS mRNA表达也增加,表达除在转录水平外,尚受到转最后调节。但iNOS活性和iNOSmRNA表达的增加远较cNOS活性和cNOSmRNA表达的增加为明显。结论:在门静脉高压症大鼠中NO过多产生主要是iNOS活性增加的结果。

To determine whether there is an overproduction of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase(iNOS) in portal hypertensive rats, and to elucidate its mechanism. Methods: Thirty-one male Sprague-Dawley rats were divided into four groups: end-to-side portacaval shunt(PCS, n=8), prehepatic portal hypertension(PHPH, n=9), intrahepatic portal hyperten-sion(IHPH, n= 7) and sham-operated controls(SO, n=7). Two weeks after surgery, the cNOS and iNOS ac-tivity in the splanchnic vessels and in the guts were measured by spectrophotometry. Reverse transcription-polymerase chain reaction(RT-PCR) was employed to measure the levels of iNOS mRNA and cNOS mRNA in these vessels and in the guts semi-quantitatively. Results: The increased iNOS expression was transcriptionally regulated, and the increased cNOS expression was regulated both transcriptionally and posttranscriptionally. Conclusions: Overproduction of NO is caused by both increased iNOS and in-creased cNOS, and especially the former; it plays a key role in the pathogenesis of hyperdynamic circula-tion in portal hypertensive rats.