Shiratori Y, Kiriyama H, Fukushi Y, Nagura T, Takada H, Hai K, Kamii K
Department of Gastroenterology and Hepatology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan.
Dig Dis Sci. 1994 Jun;39(6):1265-72. doi: 10.1007/BF02093792.
To elucidate the role of Kupffer cells in ischemia-reperfusion-induced hepatic injury, hepatic injury induced by ischemia-reperfusion was analyzed after modulation of Kupffer cell function. Ischemia of the liver was performed by occlusion of both the portal vein and hepatic artery, which enter into the left lateral and median lobes of the liver. Blood flow in the ischemic lobe was reduced, in contrast to an increased blood flow in the nonischemic lobe during occlusion of the veins. Although hepatocyte damage was not demonstrated by ischemia for < 60 min, hepatic injury was found after reperfusion of the liver, and activation of Kupffer cells was morphologically demonstrated by electron microscopies. Suppression of Kupffer cells, induced by previous administration of gadolinium chloride or latex particles, reduced the grade of hepatic injury induced by ischemia-reperfusion. On the other hand, stimulation of Kupffer cell phagocytosis, induced by administration of latex particles at the time of reperfusion, aggravated the ischemia-reperfusion-induced hepatotoxicity, which was then reduced by simultaneous administration of superoxide dismutase. Kupffer cells, isolated from the rats treated with the ischemia-reperfusion procedure, have been found to release increased amounts of oxygen radical intermediates. These results suggest that hepatic injury induced by ischemia-reperfusion is modulated by the function of Kupffer cells and that superoxide anion released from Kupffer cells could play an important role in ischemia-reperfusion hepatic injury.
为阐明库普弗细胞在缺血再灌注诱导的肝损伤中的作用，在调节库普弗细胞功能后，分析了缺血再灌注诱导的肝损伤。通过阻断进入肝脏左外侧叶和中叶的门静脉和肝动脉来造成肝脏缺血。在静脉阻断期间，缺血叶的血流减少，而未缺血叶的血流增加。尽管缺血60分钟以内未显示肝细胞损伤，但肝脏再灌注后发现了肝损伤，并且通过电子显微镜在形态学上证实了库普弗细胞的活化。预先给予氯化钆或乳胶颗粒诱导的库普弗细胞抑制，降低了缺血再灌注诱导的肝损伤程度。另一方面，再灌注时给予乳胶颗粒诱导的库普弗细胞吞噬作用刺激，加重了缺血再灌注诱导的肝毒性，而同时给予超氧化物歧化酶可减轻这种毒性。从接受缺血再灌注处理的大鼠分离出的库普弗细胞，已发现其释放的氧自由基中间体数量增加。这些结果表明，缺血再灌注诱导的肝损伤受库普弗细胞功能调节，并且库普弗细胞释放的超氧阴离子可能在缺血再灌注肝损伤中起重要作用。
