Protective effects of recombinant human growth hormone on cirrhotic rats.
OBJECTIVE
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 (R(T)) by (125)I-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 (R(T)) and the expression of GHR mRNA in vivo. R(T) in group A (72+/-12 fmol/mg protein) was significantly higher than that in group C (31+/-4 fmol/mg protein) (P<0.05). R(T) in group B (80+/-9 fmol/mg protein) increased markedly compared to group A (P<0.05). R(T) 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 1 029+/-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 cmH(2)O vs 14.4+/-2.0 cmH(2)O) (P<0.05).


CONCLUSIONS
Pharmacological doses of rhGH can increase R(T) and GHR mRNA expression, ameliorate liver functions, repress fibrosis and decline portal hypertension, suggesting it has potentially clinical usage as a hepatotropic factor.
Chen
Shuang
S
Department of General Surgery, Sun Yat-Sen Memorial Hospital, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China. mdchens@yahoo.com
Wang
Hong-Tao
HT
Yang
Bin
B
Fu
Yu-Ru
YR
Ou
Qing-Jia
QJ
D000818:Animals; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide
D013853:Thioacetamide; D019382:Human Growth Hormone