Deleted form of hepatocyte growth factor ameliorates the mortality rate ofsevere thermal injury in rats

Background. The modulating effects of the deleted form of hepatocyte growth factor (dHGF) on burn-induced mortality rates and hepatic protein synthesi s were studied in rats. Methods. Rats were anesthetized, subjected to a 40% full-thickness scald bu rn, and divided into 2 groups receiving dHGF and vehicle. Results. In normal rats, dHGF-treatment (1 mg/kg intravenously, twice daily )for 5 days increased the circulating plasma volume. In burned rats that we re receiving vehicle, the survival rate on day 23 after the burn was 27%. T he serum albumin levels were decreased and did not reverse to the normal le vels until day 23 after the burn. Serum aa-concentration in the injured rat s was increased, whereas serum levels of transferrin, total protein, and hi gh-density lipoprotein-cholesterol were decreased. The treatment of animals with dHGF (1 mg/kg intravenously, 3 times daily) for 3 days increased the survival rate on day 23 by 64%. In the animals treated with dHGF for 3 or 6 days, serum alpha(1)-, alpha(2)-, and beta-globulin concentrations were in creased by the dHGF treatment. The serum levels of albumin transferrin, tot al protein, and high-density lipoprotein-cholesterol reversed to normal lev els or higher: Conclusions. Our data show that dHGF treatment may attenuate the decrease o f the circulating plasma volume after burn and reduce a high risk of burn s hock. it is also indicated that dHGF accelerates synthesis of not only acut e-phase reactants but also other hepatic proteins such as albumin and trans ferrin on severe burn injury. These findings suggest that the appropriate u pregulation of hepatic protein synthesis induced by dHGF may accelerate the physiologic recovery process after thermal injury and contribute to amelio rating the burn-induced death.