Prevention by chlorpromazine of ischemic liver cell death.
Prevention by chlorpromazine of ischemic liver cell death.
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发表时间：
1977-09
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通讯作者：
K. Chien;J. Abrams;R. Pfau;J. Farber
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作者：
K. Chien;J. Abrams;R. Pfau;J. Farber
通过阻断大鼠肝脏左外叶和中叶的门静脉和肝动脉血供来产生缺血肝组织。如果在缺血2 - 3小时后，通过移除钳夹建立了向肝脏的回流，则24小时后三分之二或更多的肝细胞在组织学上死亡。在诱导缺血前30分钟用氯丙嗪（20 mg/kg）预处理长达3小时，几乎完全防止了这种缺血性细胞死亡。如果动物再存活24小时而不进行进一步处理，48小时时肝细胞坏死的程度仍明显低于未处理的缺血对照组。在诱导缺血后和再流开始前立即给予氯丙嗪可减少但不能完全防止缺血性细胞死亡，如在24小时测定的。氯丙嗪的这种保护作用通过治疗动物在缺血3小时后再生细胞ATP水平的能力得到证实。此外，氯丙嗪显示出显着降低总肝细胞和线粒体钙离子含量的增加，伴随着血流恢复到不可逆的损伤的肝细胞。氯丙嗪的保护作用不能归因于对肝细胞缺血的速率或程度的任何影响，也不能归因于对阻塞解除后的灌注模式的任何影响，因此可以得出结论，氯丙嗪的作用必须是对细胞对缺血本身反应的某些成分的作用。这一行动的可能基础进行了讨论。
Ischemic liver tissue was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of rat liver. If, after 2 to 3 hours of ischemia, reflow to the liver was established by removing the clamp, two-thirds or more of the liver cells were histologically dead 24 hours later. Pretreatment with chlorpromazine (20 mg/kg) 30 minutes before inducing ischemia for up to 3 hours virtually completely prevented this ischemic cell death. If the animals were kept alive for an additional 24 hours with no further treatment, the extent of liver cell necrosis at 48 hours was still markedly less than that seen in the untreated ischemic controls. Administration of chlorpromazine after induction of ischemia and immediately prior to the onset of reflow reduced but did not completely prevent ischemic cell death as determined at 24 hours. This protective action of chlorpromazine was confirmed by the ability of the treated animals to regenerate cellular ATP levels after 3 hours of ischemia. In addition, chlorpromazine was shown to significantly reduce the increases in total liver cell and mitochondrial calcium ion contents that accompany the return of blood flow to irreversibly injured liver cells. The protective effect of chlorpromazine could not be attributed to any effect either on the rate or extent to which the liver cells became ischemic or on the perfusion patterns following release of the obstruction, and it is concluded that the action of chlorpromazine must be on some component(s) of the reaction of the cells to the ischemia itself. The possible basis of this action is discussed.