Wang Hong-Tao, Chen Shuang, Wang Jie, Ou Qing-Jia, Liu Chao, Zheng Shu-Sen, Deng Mei-Hai, Liu Xiao-Ping
Department of Hepato-biliary Surgery, Sun Yat-Sen Memorial Hospital, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China.
World J Gastroenterol. 2003 Apr;9(4):765-70. doi: 10.3748/wjg.v9.i4.765.
To investigate the expression of growth hormone receptor (GHR) and mRNA of GHR in cirrhotic livers of rats with the intension to find the basis for application of recombinant human growth hormone (rhGH) to patients with liver cirrhosis.
Hepatic cirrhosis was induced in Sprague-Dawley rats by administration of thioacetamide intraperitoneally for 9-12 weeks. Collagenase IV was perfused in situ for isolation of hepatocytes. The expression of GHR and its mRNA in cirrhotic livers was studied with radio-ligand binding assay, RT-PCR and digital image analysis.
One class of specific growth hormone-binding site, GHR, was detected in hepatocytes and hepatic tissue of cirrhotic livers. The binding capacity of GHR (R(T), fmol/mg protein) in rat cirrhotic liver tissue (30.8+/-1.9) was significantly lower than that in normal control (74.9+/-3.9) at the time point of the ninth week after initiation of induction of cirrhosis (n=10, P<0.05), and it decreased gradually along with the accumulation of collagen in the process of formation and development of liver cirrhosis (P<0.05). The number of binding sites (X10(4)/cell) of GHR on rat cirrhotic hepatocytes (0.86+/-0.16) was significantly lower than that (1.28+/-0.24) in control (n=10, P<0.05). The binding affinity of GHR among liver tissue, hepatocytes of various groups had no significant difference (P>0.05). The expression of GHR mRNA (riOD, pixel) in rat cirrhotic hepatic tissues (23.3+/-3.1) was also significantly lower than that (29.3+/-3.4) in normal control (n=10, P<0.05).
The growth hormone receptor was expressed in a reduced level in liver tissue of cirrhotic rats, and lesser expression of growth hormone receptors was found in a later stage of cirrhosis. The reduced expression of growth hormone receptor was partly due to its decreased expression on cirrhotic hepatocytes and the reduced expression of its mRNA in cirrhotic liver tissue.
研究生长激素受体（GHR）在肝硬化大鼠肝脏中的表达及GHR mRNA情况，为重组人生长激素（rhGH）应用于肝硬化患者寻找依据。
采用腹腔注射硫代乙酰胺9 - 12周诱导Sprague-Dawley大鼠肝硬化。原位灌注IV型胶原酶分离肝细胞。采用放射性配体结合试验、逆转录聚合酶链反应（RT-PCR）及数字图像分析技术研究肝硬化肝脏中GHR及其mRNA的表达。
在肝硬化肝脏的肝细胞和肝组织中检测到一类特异性生长激素结合位点，即GHR。肝硬化诱导开始后第9周时，大鼠肝硬化肝组织中GHR的结合容量（R(T)，fmol/mg蛋白）为(30.8±1.9)，显著低于正常对照组(74.9±3.9)（n = 10，P < 0.05），且在肝硬化形成和发展过程中随胶原沉积逐渐降低（P < 0.05）。大鼠肝硬化肝细胞上GHR的结合位点数（×10⁴/细胞）为(0.86±0.16)，显著低于对照组(1.28±0.24)（n = 10，P < 0.05）。各组织组间GHR的结合亲和力无显著差异（P > 0.05）。大鼠肝硬化肝组织中GHR mRNA的表达（riOD，像素）为(23.3±3.1)，也显著低于正常对照组(29.3±3.4)（n = 10，P < 0.05）。
肝硬化大鼠肝组织中生长激素受体表达水平降低，且在肝硬化后期生长激素受体表达更低。生长激素受体表达降低部分归因于肝硬化肝细胞上其表达减少以及肝硬化肝组织中其mRNA表达降低。
