Protective effects of recombinant human growth hormone on cirrhotic rats

摘要

AIM: To investigate the effects and molecular mechanisms of recombinant human growth hormone (rhGH) on protecting liver function and alleviating portal hypertension of liver cirrhotic rats.METHODS: Liver cirrhosis of male Sprague-Dawley rats was induced by administration of thioacetamide. The rats with or without liver cirrhosis were randomly divided into four groups. Group A consisted of the normal rats was treated with normal saline (NS), group B consisted of the normal rats was treated with rhGH, group C consisted of cirrhotic rats was treated with NS, and group D consisted of cirrhotic rats was treated with rhGH. The rats of different groups were subcutaneously injected with 0.5 mL of NS or 333 ng/kg of rhGH daily for 7 d. After treatments, the following parameters were examined, including GH-binding capacity (RT) by ¹²⁵I-hGH binding, growth hormone receptor mRNA(GHR mRNA) expression by RT-PCR, relative content of collagen (RCC) by histomorphomertry, and level of malon-dialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue by thiobarbituric acid reaction and pyrogallic acid self-oxidation, respectively. Serum albumin (ALB), alanine transaminase (ALT) and portal vein pressure (PVP) were also examined.RESULTS: rhGH up-regulated both the GH-binding capacity (RT) and the expression of GHR mRNA in vivo. RT in group A (72 ± 12 fmol/mg protein) was significantly higher than that in group C (31 ± 4 fmol/mg protein) (P < 0.05). RT in group B (80 ± 9 fmol/mg protein) increased markedly compared to group A (P < 0.05). RT in group D (40 ± 7 fmol/mg protein) raised remarkably compared with group C (P < 0.05), but less than that in group A, and there was no significant GH binding affinity contrast (Kd) change. The GHR mRNA level (iOD, pixel) in group A (29 ± 3) was significantly higher than that in group C (23 ± 3) (P < 0.05). GHR mRNA levels were significantly raised in group B (56 ± 4) and group D (42 ± 8) compared with groups A and C (29 ± 3 and 23 ± 3, respectively) (P < 0.05). Compared with the normal liver, MDA level was higher and SOD level was lower in cirrhotic livers. After rhGH treatment, MDA level was significantly declined to 12.0 ± 2.2 nmol/mg protein and SOD was raised to 1029 ± 76 U/mg protein in group D (P < 0.05). ALB levels in groups B and D (42 ± 7 g/L and 37 ± 7 g/L, respectively) were significantly raised compared with those in groups A and C (35 ± 5 g/L and 29 ± 4 g/L, respectively) (P < 0.05). ALT level was markedly lower in group D (69 ± 7 U/L) compared to group C (89 ± 15 U/L) (P < 0.05), and close to group A (61 ± 10 U/L). RCC in group C (22.30% ± 3.86%) was significantly higher than that in group A (1.14% ± 0.21%) and group D (14.70% ± 2.07%) (P < 0.05). In addition, rhGH markedly alleviated portal hypertension in liver cirrhotic rats (group D vs C, 9.3 ± 1.5 cmH2O vs 14.4 ± 2.0 cmH2O) (P < 0.05).CONCLUSION: Pharmacological doses of rhGH can increase RT and GHR mRNA expression, ameliorate liver functions, repress fibrosis and decline portal hypertension, suggesting it has potentially clinical usage as a hepatotropic factor.