Mohammed Nasser A, Abd El-Aleem Seham, Appleton Ian, Maklouf Madiha M, Said Mahmoud, McMahon Raymond F T
Departments of Tropical Medicine and General Medicine, Minia University, Minia, Egypt.
J Pathol. 2003 Aug;200(5):647-55. doi: 10.1002/path.1377.
Several mediators of systemic vasodilatation in liver cirrhosis have been reported. Among these is nitric oxide (NO), which has been proposed as one of the main mediators. In this study, sera and liver biopsies were analysed from 15 patients with clinically and pathologically diagnosed liver cirrhosis. In addition, sera from seven and liver biopsies from three healthy controls were used. Serum levels of nitrite (the end product of NO) were measured using the Griess reaction and the expression of the inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (ecNOS) proteins was investigated using immunohistochemistry. This study shows that serum nitrite levels (94 +/- 9.8 micro mol/l) in cirrhotic patients were significantly (p < 0.05) increased in comparison with the controls (36.6 +/- 11.03 micro mol/l). iNOS was completely absent from the control group but was highly expressed in the livers from the cirrhotic group. iNOS was seen mainly in the inflammatory cells infiltrating the portal tracts, blood monocyte-like cells, hepatocytes, sinusoidal cells, and endothelial cells. However, expression of ecNOS was only seen in the vascular endothelial cells of both the control and the cirrhotic groups, but was much higher in the latter. It is therefore clear that NO is augmented in cirrhotic patients and it is mainly produced by induction of iNOS. Moreover, NO up-regulation is dependent on the inflammatory stage of liver cirrhosis. ecNOS production could be a normal chronic adaptation mechanism of the endothelium to the chronically increased splanchnic blood flow secondary to portal hypertension. In the near future, the appropriate inhibition of NO activity by using NOS-active agents may provide a novel strategy for the treatment of patients with liver cirrhosis.
已有报道称肝硬化患者体内存在多种导致全身血管舒张的介质。其中一氧化氮（NO）被认为是主要介质之一。在本研究中，对15例临床和病理诊断为肝硬化的患者进行了血清和肝活检分析。此外，还使用了7名健康对照者的血清和3名健康对照者的肝活检样本。采用格里斯反应测定血清亚硝酸盐水平（NO的终产物），并通过免疫组织化学研究诱导型一氧化氮合酶（iNOS）和组成型一氧化氮合酶（ecNOS）蛋白的表达。本研究表明，肝硬化患者的血清亚硝酸盐水平（94±9.8微摩尔/升）与对照组（36.6±11.03微摩尔/升）相比显著升高（p<0.05）。对照组中完全没有iNOS，但在肝硬化组的肝脏中高表达。iNOS主要见于浸润汇管区的炎性细胞、血液单核细胞样细胞、肝细胞、窦状隙细胞和内皮细胞。然而，ecNOS的表达仅见于对照组和肝硬化组的血管内皮细胞，但在后者中表达更高。因此，很明显肝硬化患者体内NO增加，且主要由iNOS的诱导产生。此外，NO的上调取决于肝硬化的炎症阶段。ecNOS的产生可能是内皮细胞对门静脉高压继发的内脏血流长期增加的一种正常慢性适应机制。在不久的将来，使用一氧化氮合酶活性药物适当抑制NO活性可能为肝硬化患者提供一种新的治疗策略。
