Pathogenesis of precirrhotic portal hypertension in alcohol-fed baboons.
Pathogenesis of precirrhotic portal hypertension in alcohol-fed baboons.
复制标题
酒精喂养狒狒肝硬化前门静脉高压症的发病机制。
DOI：
10.1016/s0016-5085(85)80146-3
复制
发表时间：
1985
期刊：
影响因子：
29.4
通讯作者：
Lieber,CS
中科院分区：
文献类型：
--
作者：
Miyakawa,H;Iida,S;Leo,MA;Greenstein,RJ;Zimmon,DS;Lieber,CS
为了研究肝硬化前门静脉高压症的机制和解剖学相关性，我们测量了24对狒狒在开腹时（门静脉）或肝静脉导管插入术（楔形压力）的门静脉压力，这些狒狒在4个月至9年的时间里，以乙醇或等热量碳水化合物（对照组）的形式喂养50%的能量。门静脉压力均未超过控制范围（2.7 ~ 13.0 cmH2O）。其余17只酒精喂养的狒狒在末端肝小静脉和邻近的窦周围有纤维组织沉积。与脂肪肝狒狒（9.6±0.9 cmH2O）和对照组（8.0±0.6 cmH2O）相比，平均门静脉压力显著增加（15.0±1.4 cmH2O），其中8只动物超过控制范围。估计肝血流量不变。酒精喂养导致脂肪肝组和脂肪肝合并纤维化组肝细胞大小增大；然而，门静脉压力与细胞大小、肝体积、肝甘油三酯和蛋白质含量的改变无关。相比之下，对于同等大小的静脉，静脉周围纤维边缘的厚度与门静脉压力之间存在显著相关性（r = 0.6666,p< 0.01）。静脉周围纤维化通常与相邻的静脉周围纤维化相关，这种病变也与门静脉压力相关。此外，如果有人假设细胞大小的增加导致继发性纤维化的压力增加，后者应该首先发生在“上游”，在中间和门静脉区。然而，连续活检标本显示纤维化首先出现在静脉周围区域，这表明，在大多数情况下，压力升高实际上是继发于静脉周围纤维化。
To study mechanisms and anatomic correlates of precirrhotic portal hypertension, we measured portal pressure either at laparotomy (in the portal vein) or by hepatic vein catheterization (wedge pressure) in 24 pairs of baboons fed 50% of energy either as ethanol or isocaloric carbohydrate (controls) for 4 mo–9 yr. On liver biopsy 7 had simple fatty liver; none had portal pressure exceeding the control range (2.7–13.0 cmH2O). The remaining 17 alcoholfed baboons had fibrous tissue deposition around the terminal hepatic venules and adjacent sinusoids. The mean portal pressure was significantly increased (15.0 ± 1.4 cmH2O) compared with the value in baboons with fatty liver (9.6 ± 0.9 cmH2O) and in controls (8.0 ± 0.6 cmH2O), with 8 animals exceeding the control range. Estimated hepatic blood flow was unchanged. Alcohol feeding resulted in increased hepatocyte size in both the fatty liver and fatty liver with fibrosis group; however, portal pressure did not correlate with alterations of cell size, liver volume, hepatic triacylglycerol, and protein contents. By contrast, for veins of comparable size, there was a significant correlation (r = 0.6666,p< 0.01) between the thickness of the perivenular fibrous rim and portal pressure. Perivenular fibrosis was commonly associated with adjacent perisinusoidal fibrosis and this lesion also correlated with portal pressure. Furthermore, i f one postulates that increased cell size causes enhanced pressure with secondary fibrosis, the latter should have first occurred “upstream,” in the mid and portal zones. Sequential biopsy specimens, however, showed that fibrosis first appeared in the perivenular areas, suggesting that, in most instances, increased pressure is in fact secondary to the perivenular fibrosis.