Effects Of Glucocorticoids Combine With Interferon-α Or Growth Hormone On Fulminant Hepatic Failure In Rats And Its Mechanisms

To investigate the effects of glucocorticoids(GC) combine with interfron-a(IFN-a) or human growth hormone (GH) on fulminant hepatic failure in rats, The D-GalN/LPS-or-CCL4-induced fulminant hepatic failure were obtained in rats.The main contents include some sections as follows:1. Glucocorticoids combine with interfron-a or growth hormone prevented the occurrence of the D-GalN/ LPS- or- CCl4 -induced fulminant hepatic failure in rats. When glucocorticoid was administered in advance at dose of 25,50 and 100 mg .kg-1, the serum bilirubin,alanine aminotransaminase and aspartate aminotransaminase levels of rats were lower than in models.Among different dose,the 50 mg .kg-1 treatment got the best efficacy; When glucocorticoid was administered 4 hours after the immune or chemical agents was given,the block of serum bilirubin,alanine aminotransaminase and aspartate aminotransaminase level elevation was still obvious , but the range is small and there were no difference between the three doses.When interfron-a was administered in advance at dose of 0.1 g,0.5 g and 1 g .kg-1, the serum bilirubin,alanine aminotransaminase and aspartate aminotransaminase levels rise were observed when interfron-a and glucocorticoids were given at the same time.the best effect was found in interferon-a at dose of 0.1 g .kg-1 and glucocorticoid at 50mg.kg-1.When growth hormone was intraperitoneously adminestered at dose of 0.1IU,0.5IU andlIU.kg-1,the serum bilirubin,alanine aminotransaminase and aspartate aminotransaminase levels of rats were prevented obviously.The prevention of liver injuries of growth hormone were better when administered with glucocorticoid. 2.The mechamisms of glucocorticoids combine with interfron-a or growth hormone on chemical-andimmune-jnduced hepatic failure.When glucocorticoid alone or combine with interfron-a or growth hormone were administered in advance,the serum tumor necroses factor-a ,interleukin-6 and interleukin-8 levels of rats were lower than in models. Serum tumor necroses factor-a ,interleukin-6 and interleukin-8 levels increased as in the model,when the medicine was geven 4 hours after the model formation.The Kupffer cells were obtained,cultured and stimulated by LPS at dose of 10 g .ml-1,and the tumor necroses factor-a levels in the supernatants were assayed by ELISA.The levels of tumor necroses factor-a inceased after 2 hours culture and the pink was found at 4 hours.When the hepatocytes were stimulated by LPS,the tumor necrosis factor-a level in the supernatants did not increase.When the glucocorticoid was added previously to the kupffer cells stimulated by LPS,the production of tumor necroses factor-a was reduced. But adding it to the culture 4 hours later, the production of tumor necroses factor-a was not blocked. When interfron-a at dose of 0.1ug,0.5ug and lug .kg"1 and growth hormone at dose of 0.1IU,0.5IU andllU .kg"1 were added at the same time to the culture,the tumor necroses factor-a lecel in the supernatants went even high. The adminestration of glucocorticoid prevented the increment of tumor necroses factor-a.The better result was found in combination of interfron-a at 0.1ug .kg"1 and glucocorticoid at 50mg .kg"1; and in combination of growth hormone at 0.5IU .kg"1 and glucocorticoid at 50mg .kg"1. In summary, the findings in our experiments showed that the administration of glucocoiticord in advance can prevent the occurrence of chemical-orimmune-inducecd fulminant hepatic failure in rats and the best result is at the dose of 50mg .kg"1 and the medicine should be given as earlier as possible. The use of interfron-a do not interfere with the action of glucocorticoid and the combination of growth hormone and glucocorticoid block the liver failure too.