Cannabinoid Type 1 Receptor Antagonism Delays Ascites Formation in Rats With Cirrhosis
Cannabinoid Type 1 Receptor Antagonism Delays Ascites Formation in Rats With Cirrhosis
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DOI：
10.1053/j.gastro.2009.01.004
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发表时间：
2009-07-01
期刊：
影响因子：
29.4
通讯作者：
Bernardi, Mauro
中科院分区：
文献类型：
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作者：
Domenicali, Marco;Caraceni, Paolo;Bernardi, Mauro
背景与目的：内源性大麻素会导致肝硬化的血流动力学异常。这是否有利于肾钠潴留和腹水形成尚不清楚。我们确定了 1 型大麻素受体拮抗作用是否可以预防腹水前肝硬化大鼠的钠潴留和腹水形成。方法：一旦肾钠处理功能受损，患有四氯化碳诱导的肝硬化的大鼠被随机接受媒介物或利莫那班（3 [第 1 组] 或 10 [第 2 组] mg.kg(-1).day(-1)），为期 2 周。每天测量尿钠排泄、钠摄入量和钠平衡。在方案结束时，评估全身血流动力学、肾血流量、腹水量和肝纤维化。结果：治疗大鼠的腹水形成（第 1 组：54%；第 2 组：10%；媒介物：90%）和体积（第 1 组：1.6 +/- 0.3 mL；第 2 组：0.5 mL；媒介物：5.5 +/- 0.8 mL）显着减少。利莫那班在第 2 周显着改善钠平衡（第 1 组：0.98 +/- 0.08 mmol；第 2 组：0.7 +/- 0.08 mmol；媒介物：3.05 +/- 0.11 mmol）。两个治疗组均显示出较低的心输出量和较高的平均动脉压、外周血管阻力和肾血流量 (P < .05)。第 2 组的肝纤维化减少了 30%（P
BACKGROUND & AIMS: Endocannabinoids contribute to hemodynamic abnormalities of cirrhosis. Whether this favors renal sodium retention and ascites formation is unknown. We determined whether cannabinoid type 1. receptor antagonism prevents sodium retention and ascites formation in preascitic cirrhotic rats. METHODS: Once renal sodium handling was impaired, rats with carbon terrachloride-induced cirrhosis were randomized to receive either vehicle or rimonabant (3 [group 1] or 10 [group 2] mg . kg(-1) . day(-1)) for 2 weeks. Natriuresis, sodium intake, and sodium balance were measured daily. At the end of the protocol, systemic hemodynamics, renal blood flow, ascites volume, and liver fibrosis were assessed. RESULTS: A significant reduction in ascites formation (group 1: 54%; group 2: 10%, vehicle: 90%) and volume (group 1: 1.6 +/- 0.3 mL; group 2: 0.5 mL; vehicle: 5.5 +/- 0.8 mL) occurred in treated rats. Rimonabant significantly improved sodium balance during week 2 (group 1: 0.98 +/- 0.08 mmol; group 2: 0.7 +/- 0.08 mmol; vehicle: 3.05 +/- 0.11 mmol). Both treated groups showed lower cardiac output and higher mean arterial pressure, peripheral vascular resistance, and renal blood flow (P < .05). Liver fibrosis was reduced in group 2 by 30% (P