Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice
Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice
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DOI：
10.1002/hep.510300102
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发表时间：
1999-07-01
期刊：
影响因子：
13.5
通讯作者：
Nakamura, T
中科院分区：
文献类型：
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作者：
Kosai, K;Matsumoto, K;Nakamura, T
脓毒症和内毒素血症与暴发性肝衰竭的发生发展有关，预后极差，死亡率高，目前尚无有效的治疗方法。本文报道肝细胞生长因子（HGF）在体内具有有效的抗凋亡作用，能有效预防内毒素诱导的小鼠暴发性肝衰竭。在腹膜内注射脂多糖（LPS）和D-半乳糖胺（GalN）之前6小时30分钟和之后3小时，用120 μ g人重组HGF或盐水腹膜内注射动物三次。给予LPS + GalN而不给予HGF，迅速导致大量肝细胞凋亡和严重的肝损伤，所有小鼠在8小时内死于肝衰竭。与此相反，人重组HGF给药强烈抑制了肝细胞凋亡和LPS + GalN诱导的肝损伤的广泛进展，75%的HGF治疗的小鼠存活。此外，HGF强烈诱导Bcl-xL表达并阻断肝中CPP 32（caspase-3）上游的凋亡信号转导，从而导致抑制大量肝细胞凋亡。我们认为，肝细胞生长因子可能有潜力，以防止暴发性肝衰竭，至少通过其强大的抗凋亡作用。
Sepsis and endotoxemia are involved in the development of fulminant hepatic failure, the prognosis of which is extremely poor and the mortality is high, with no available effective therapy Here, wt report that hepatocyte growth factor (HGF) exerts potent antiapoptotic effects in vivo and effectively prevents endotoxin-induced fulminant hepatic failure in mice. The animals were intraperitoneally injected three times with 120 mu g human recombinant HGF or saline 6 hours and 30 minutes before and 3 hours after an intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (GalN). Administration of LPS + GalN, without HGF, rapidly led to massive hepatocyte apoptosis and severe liver injury and all mice died of hepatic failure within 8 hours. In contrast, administration of human recombinant HGF strongly suppressed extensive progress of hepatocyte apoptosis and the liver injury induced by LPS + GalN, and 75% of the HGF-treated mice survived. Moreover, HGF strongly induced Bcl-xL expression and blocked apoptotic signal transduction upstream of CPP32 (caspase-3) in the liver, thereby leading to inhibition of massive hepatocyte apoptosis. We suggest that HGF may well have the potential to prevent fulminant hepatic failure, at least through its potent antiapoptotic action.