Protective effects of recombinant human growth hormone on cirrhotic rats

AIM: To investigate the effects and molecular mechanismsof recombinant human growth hormone (rhGH) onprotecting liver function and alleviating portal hypertensionof liver cirrhotic rats.METHODS: Liver cirrhosis of male Sprague-Dawley ratswas induced by administration of thioacetamide. The ratswith or without liver cirrhosis were randomly divided intofour groups. Group A consisted of the normal rats wastreated with normal saline (NS), group B consisted of thenormal rats was treated with rhGH, group C consisted ofcirrhotic rats was treated with NS, and group D consistedof cirrhotic rats was treated with rhGH. The rats of differentgroups were subcutaneously injected with 0.5 mL of NS or333 ng/kg of rhGH daily for 7 d. After treatments, thefollowing parameters were examined, including GH-bindingcapacity (RO by 12SI-hGH binding, growth hormone receptormRNA(GHR mRNA) expression by RT-PCR, relative contentof collagen (RCC) by histomorphomertry, and level ofmalon-dialdehyde (MDA) and superoxide dismutase (SOD)in liver tissue by thiobarbituric acid reaction and pyrogallicacid 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(R0 and the expression of GHR mRNA in vivo. RT in groupA (72+12 fmol/mg protein) was significantly higher thanthat in group C (31+4 fmol/mg protein) (P<0.05). RT ingroup B (80+9 fmol/mg protein) increased markedlycompared to group A (P<0.05). RT in group D (40+7 fmol/mgprotein) raised remarkably compared with group C (P<0.05),but less than that in group A, and there was no significantGH binding affinity contrast (Kd) change. The GHR mRNAlevel (iOD, pixel) in group A (29+3) was significantly higherthan that in group C (23+3) (P<0.05). GHR mRNA levelswere 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 cirrhoticlivers. After rhGH treatment, MDA level was significantlydeclined to 12.0+2.2 nmol/mg protein and SOD was raisedto 1029+76 U/rag protein in group D (P<0.05). ALB levelsin groups B and D (42+7 g/L and 37+7 g/L, respectively)were significantly raised compared with those in groups Aand 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 togroup A (61+10 U/L). RCC in group C (22.30+3.86%) wassignificantly higher than that in group A (1.14+0.21%) andgroup D (14.70+2.07%) (P<0.05). In addition, rhGHmarkedly alleviated portal hypertension in liver cirrhoticrats (group D vsC, 9.3+1.5 cmH20 vs 14.4+2.0 cmH20)(P<0.05).CONCLUSION: Pharmacological doses of rhGH canincrease RT and GHR mRNA expression, ameliorate liverfunctions, repress fibrosis and decline portal hypertension,suggesting it has potentially clinical usage as a hepatotropicfactor.