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Expression of growth hormone receptor and its mRNA in hepatic cirrhosis

机译:生长激素受体及其mRNA在肝硬化中的表达

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AIM: 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. METHODS: 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. RESULTS: 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 (xl0~4/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). CONCLUSION: 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.
机译:目的:探讨意图在大鼠肝硬化肝脏中生长激素受体(GHR)的表达和GHR mRNA的表达,为重组人生长激素(rhGH)在肝硬化患者中的应用提供依据。方法:通过腹腔注射硫代乙酰胺9-12周,在Sprague-Dawley大鼠中诱发肝硬化。原位灌注胶原酶IV以分离肝细胞。通过放射性配体结合试验,RT-PCR和数字图像分析研究了GHR及其在肝硬化肝脏中的mRNA表达。结果:在肝硬化肝细胞和肝组织中检测到一类特异性生长激素结合位点GHR。诱导开始后第九周,大鼠肝硬化肝组织中GHR(R_T,fmol / mg蛋白)的结合能力(30.8 + -1.9)明显低于正常对照组(74.9 + -3.9)。肝硬化的发生(n = 10,P <0.05),并在肝硬化形成和发展过程中随着胶原蛋白的积累而逐渐降低(P <0.05)。大鼠肝硬化肝细胞中GHR的结合位点数(x10〜4 /细胞)(0.86 + -0.16)显着低于对照组(n = 10,P <0.05)(1.28 + -0.24)。各组肝组织,肝细胞之间GHR的结合亲和力无显着性差异(P> 0.05)。大鼠肝硬化肝组织中GHR mRNA的表达(riOD,像素)(23.3 + -3.1)也显着低于正常对照组(n = 10,P <0.05)(29.3 + -3.4)。结论:肝硬化大鼠肝组织中生长激素受体的表达降低,而在肝硬化后期,生长激素受体的表达较少。生长激素受体表达的降低部分是由于其在肝硬化肝细胞中的表达降低以及其在肝硬化肝组织中的mRNA表达的降低。

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