Ackerman Z, Karmeli F, Amir G, Rachmilewitz D
Department of Medicine, Hadassah University Hospital, Mount Scopus, Hebrew University Hadassah Medical School, Jerusalem, Israel.
J Hepatol. 1996 Apr;24(4):478-86. doi: 10.1016/s0168-8278(96)80169-3.
BACKGROUND/METHODS: Vasoactive substances may have a role in the pathogenesis of functional renal abnormalities in patients with cirrhosis. We determined renal vasoactive mediators in rats with portal hypertension since the balance in each part of the kidney between the vasodilator activity of prostaglandin E2 and the vasospastic activity of thromboxane A2, leukotriene B4, leukotriene C4, endothelin-1 and platelet activating factor may determine renal function. Rats with partial portal vein ligation (n = 7), complete bile duct ligation (n = 6) and sham operated (n = 10) were studied. Three weeks following surgery renal function tests, including fractional excretion of sodium [Fe(Na)] were measured. Rats were anesthetized, splenic pulp pressure was measured, kidneys were removed, and cortex, medulla and papilla were separated and homogenized for determination of prostaglandin E2, thromboxane B2, leukotriene B4, leukotriene C4 and endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation.
Pulp pressure was > 13 mmHg in portal vein ligated and bile duct ligated and 6 mmHg in sham operated rats. In bile duct ligated rats there was a 70% decrease in Fe(Na) and a significant decrease in cortical and papillary prostaglandin E2, whereas cortical thromboxane B2 and platelet activating factor activity in the cortex, medulla and papilla were double that of sham operated rats. A similar but insignificant trend of changes was found in portal vein ligated rats. Medullary leukotriene B4 was significantly decreased in bile duct ligated rats. Papillary leukotriene B4 was not detected in bile duct ligated and portal vein ligated rats. Renal leukotriene C4 generation in the three groups was either unchanged (papilla) or beyond detection (cortex and medulla). Medullary and papillary endothelin-1 in portal vein ligated and bile duct ligated rats were 178%-130% higher than in sham operated rats. A significant negative correlation was found between Fe(Na) and cortical and medullary thromboxane B2 generation and medullary platelet activating factor activity.
背景/方法：血管活性物质可能在肝硬化患者功能性肾脏异常的发病机制中起作用。我们测定了门静脉高压大鼠的肾血管活性介质，因为肾脏各部分中前列腺素E2的血管舒张活性与血栓素A2、白三烯B4、白三烯C4、内皮素-1和血小板活化因子的血管痉挛活性之间的平衡可能决定肾功能。研究了部分门静脉结扎（n = 7）、完全胆管结扎（n = 6）和假手术（n = 10）的大鼠。术后三周测量包括钠分数排泄[Fe(Na)]在内的肾功能测试指标。将大鼠麻醉，测量脾髓压力，取出肾脏，分离皮质、髓质和乳头并匀浆，通过放射免疫测定法（ng/g）测定前列腺素E2、血栓素B2、白三烯B4、白三烯C4和内皮素-1，并通过血小板聚集测定血小板活化因子活性（pg/10 mg）。
门静脉结扎和胆管结扎大鼠的髓压>13 mmHg，假手术大鼠为6 mmHg。在胆管结扎大鼠中Fe(Na)降低了70%，皮质和乳头前列腺素E2显著降低，而皮质、髓质和乳头中的皮质血栓素B2和血小板活化因子活性是假手术大鼠的两倍。在门静脉结扎大鼠中发现了类似但不显著的变化趋势。胆管结扎大鼠的髓质白三烯B4显著降低。在胆管结扎和门静脉结扎大鼠中未检测到乳头白三烯B4。三组中肾脏白三烯C4的生成要么未改变（乳头），要么无法检测到（皮质和髓质）。门静脉结扎和胆管结扎大鼠的髓质和乳头内皮素-1比假手术大鼠高178% - 130%。发现Fe(Na)与皮质和髓质血栓素B2生成以及髓质血小板活化因子活性之间存在显著负相关。
1）在胆管结扎大鼠中，肾内血栓素A2和血小板活化因子生成增加可能导致肾钠排泄减少。2）胆管结扎大鼠肾内前列腺素E2降低和肾内内皮素-1含量增加的作用尚不清楚。3）门静脉结扎和胆管结扎大鼠的肾脏白三烯生成要么减少，要么无法检测到。
