Ma Z, Miyamoto A, Lee S S
Gastroenterology Research Group, University of Calgary, Alberta, Canada.
Gastroenterology. 1996 Apr;110(4):1191-8. doi: 10.1053/gast.1996.v110.pm8613009.
BACKGROUND & AIMS: Attenuated ventricular contractility has been documented in cirrhosis, but the pathogenesis remains unclear. The beta-adrenergic receptor system is critical in modulating cardiac contraction. Therefore, the aim of this study was to clarify beta-adrenoceptor signaling function in a rat model of cirrhosis.
Cirrhosis was induced by bile duct ligation, whereas controls underwent a sham operation. Myocardial contractility was studied by measuring isolated left ventricular papillary muscle contraction under isoproterenol stimulation. Beta-Adrenoceptor signaling was evaluated by measuring adenosine 3',5'-cyclic monophosphate generation after stimulation with isoproterenol, sodium fluoride, and forskolin. Guanosine triphosphate-binding protein expression from ventricular plasma membranes was determined by Western blots to measure G(s)alpha, Gi2alpha, and G(common)beta, respectively.
Maximum papillary muscle contractile responses in control and cirrhotic rats were 113% +/- 3% and 70% +/- 2% of basal, respectively (P<0.01), with no significant differences in the dose-inducing half-maximal response. Adenosine 3', 5'-cyclic monophosphate generation after stimulation with all three agents was significantly lower in cirrhotic compared with control rat membranes. G(s)alpha and Gi2alpha expression was significantly reduced in cirrhotics compared with controls, but G(common)beta expression remained unchanged.
These data showed cardiac contractile impairment in cirrhosis, associated with altered beta-adrenergic receptor signaling function and guanine nucleotide-binding protein expression. These factors may play an important role in the pathogenesis of cirrhotic cardiomyopathy.
肝硬化患者已被证实存在心室收缩力减弱，但发病机制仍不清楚。β-肾上腺素能受体系统在调节心脏收缩中起关键作用。因此，本研究旨在阐明肝硬化大鼠模型中β-肾上腺素能受体信号传导功能。
通过胆管结扎诱导肝硬化，而对照组进行假手术。通过测量异丙肾上腺素刺激下离体左心室乳头肌收缩来研究心肌收缩力。通过测量异丙肾上腺素、氟化钠和福斯高林刺激后3',5'-环磷酸腺苷的生成来评估β-肾上腺素能受体信号传导。通过蛋白质免疫印迹法测定心室质膜中鸟苷三磷酸结合蛋白的表达，分别测量G(s)α、Gi2α和G(共同)β。
对照组和肝硬化大鼠乳头肌的最大收缩反应分别为基础值的113%±3%和70%±2%（P<0.01），诱导半数最大反应的剂量无显著差异。与对照大鼠膜相比，肝硬化大鼠膜在所有三种药物刺激后3',5'-环磷酸腺苷的生成均显著降低。与对照组相比，肝硬化患者G(s)α和Gi2α表达显著降低，但G(共同)β表达保持不变。
这些数据表明肝硬化患者存在心脏收缩功能受损，与β-肾上腺素能受体信号传导功能改变和鸟嘌呤核苷酸结合蛋白表达有关。这些因素可能在肝硬化性心肌病的发病机制中起重要作用。
