Protective effects of recombinant human growth hormone on cirrhotic rats.

Abstract

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 (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).

CONCLUSION:

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.

• Authors: Shuang Chen, Hong-Tao Wang, Bin Yang, Yu-Ru Fu, Qing-Jia Ou
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 10 Issue 19 Pg. 2894-7 (Oct 01 2004) ISSN: 1007-9327 [Print] United States
• PMID: 15334695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Thioacetamide
• Human Growth Hormone

Topics

• Animals
• Human Growth Hormone (therapeutic use)
• Humans
• Liver Cirrhosis, Experimental (chemically induced, drug therapy)
• Male
• Rats
• Rats, Sprague-Dawley
• Thioacetamide