Seda H W, Hughes R D, Gove C D, Williams R
Hepatology. 1984 Jan-Feb;4(1):74-9. doi: 10.1002/hep.1840040113.
Among the toxins accumulating in the circulation of patients with fulminant hepatic failure (FHF) are substances which inhibit leucocyte ouabain-sensitive sodium transport. A similar inhibition of brain Na+,K+-ATPase could lead to both coma and cerebral edema found in these patients which are associated with high mortality. In this study, we have investigated the effect of sera from FHF on normal rat brain Na+,K+-ATPase activity in vitro. Serum from patients with FHF significantly decreased the ouabain-sensitive Na+,K+-ATPase activity (13.58 +/- S.D. 2.60 mumoles Pi mg protein-1 hr-1) in the rat brain membrane preparation in vitro as compared to normal serum (20.33 +/- 3.24 mumoles Pi mg protein-1 hr-1, p less than 0.001). A final serum dilution of 1 in 40 was required to abolish the inhibition of Na+,K+-ATPase activity. Cerebrospinal fluid obtained at postmortem from FHF patients also contained the inhibitory substances. Serum from patients in coma due to decompensated chronic liver disease inhibited the Na+,K+-ATPase activity (17.25 +/- 1.37 mumoles Pi mg protein-1 hr-1), but this was less marked than with FHF serum. Hence, the inhibition of brain Na+,K+-ATPase by substances accumulating in the serum in FHF may be important in the pathogenesis of hepatic coma.
暴发性肝衰竭（FHF）患者循环系统中蓄积的毒素里，有些物质会抑制白细胞对哇巴因敏感的钠转运。对脑钠钾ATP酶的类似抑制作用可能会导致这些患者出现昏迷和脑水肿，而这两者都与高死亡率相关。在本研究中，我们调查了FHF患者的血清对正常大鼠脑钠钾ATP酶体外活性的影响。与正常血清（20.33±3.24微摩尔无机磷/毫克蛋白/小时）相比，FHF患者的血清在体外大鼠脑膜制备中显著降低了对哇巴因敏感的钠钾ATP酶活性（13.58±标准差2.60微摩尔无机磷/毫克蛋白/小时，p<0.001）。需要将血清最终稀释至1:40才能消除对钠钾ATP酶活性的抑制。FHF患者死后获得的脑脊液中也含有这种抑制性物质。失代偿性慢性肝病所致昏迷患者的血清抑制了钠钾ATP酶活性（17.25±1.37微摩尔无机磷/毫克蛋白/小时），但不如FHF患者血清的抑制作用明显。因此，FHF患者血清中蓄积的物质对脑钠钾ATP酶的抑制作用可能在肝性昏迷的发病机制中起重要作用。
