Hepatocellular transplantation for experimental ischemic acute liver failure in dogs.
Hepatocellular transplantation for experimental ischemic acute liver failure in dogs.
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肝细胞移植治疗犬实验性缺血性急性肝衰竭。
DOI：
10.1016/0022-4804(80)90064-5
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
J. Najarian
中科院分区：
文献类型：
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作者：
B. Sommer;D. Sutherland;R. L. Simmons;J. Najarian
如果在外源性肝再生期间能够提供代谢支持，则急性肝衰竭的恢复是可能的。在狗中测试了移植的分散的自体肝细胞改变实验性缺血性急性肝衰竭的过程的能力。在建立侧-侧门腔分流后48小时和左外侧肝叶切除术后立即通过阻断近端门静脉和肝动脉中的血流诱导肝衰竭。第1组中的犬存在缺血性损伤，但未进行治疗。第二组在缺血期后接受脾内肝细胞移植（26 ± 4x × 108个完整细胞）。在肝缺血期间，从切除的肝叶制备用于移植的细胞。第三组犬在肝缺血和脾主动脉结扎后接受自体肝细胞脾内移植（26 = 3 × 108个完整细胞）。在缺血前和缺血后连续测定血清胆红素、血清谷丙转氨酶、乳酸脱氢酶和碱性磷酸酶，结果显示三组的肝损伤程度相似，但III组的存活率更好。只有20%的非移植动物（第I组）存活了10天。死亡动物肝脏组织学显示终末肝中央静脉周围出血性坏死情况。移植并没有改善脾动脉化犬的存活率，死亡犬的组织学检查显示肺梗死和肝细胞栓塞引起的额外肝损伤。相反，脾内肝细胞移植前脾动脉结扎的动物中有70%在10天时存活。结扎脾动脉减少了肝细胞逃逸到脾静脉中的趋势，并且由于侧支循环，脾脏保持活力。在组织学检查中，肝细胞在移植后24小时、2周和4周时在脾实质中很容易被识别。总之，脾内肝细胞为犬从其他致死性缺血诱导的急性肝衰竭中恢复提供了足够的代谢支持。
Recovery from acute liver failure is possible if metabolic support can be provided during the period of exogenous liver regeneration. The ability of transplanted dispersed autologous hepatocytes to alter the course of experimental ischemic acute liver failure in dogs was tested. Liver failure was induced by occlusion of blood flow in the proximal portal vein and hepatic artery(s) 48 hr after creation of a side to side portacaval shunt and immediately after a left lateral hepatic lobectomy. Dogs in Group 1 had ischemic injury with no treatment. Dogs in Group II received intrasplenic autotransplants of hepatocytes (26 ± 4x × 108intact cells) after the ischemic period. Cells for transplantation were prepared from the excised lobe during the period of liver ischemia. Dogs in Group III received intrasplenic transplants of autologous hepatocytes (26 = 3 × 108intact cells) after liver ischemia and after ligation of the main splenic artery. Serum bilirubin, serum glutamic oxalocetic transaminase, lactate dehydrogenase, and alkaline phosphatase were measured before and serially after ischemia, and showed that the degree of liver injury in all three groups was similar, although survival in Group III was better. Only 20% of nontransplanted animals (Group I) survived 10 days. Liver histology in animals that died showed hemorrhagic necrosis situation around the terminal hepatic central veins. Transplantation did not improve survival in dogs with arterialized spleens and histological examination of dogs that died showed pulmonary infarcts and additional liver injury from embolization of hepatocytes. In contrast, 70% of the animals undergoing splenic artery ligation before intrasplenic transplantation of hepatocytes were alive at 10 days. Ligation of the splenic artery reduced the tendency for hepatocytes to escape into the splenic vein and the spleen remained viable due to collateral circulation. On histological examination, hepatocytes were readily identified in the splenic parenchyma at 24 hr. 2 and 4 weeks after transplantation. In conclusion, intrasplenic hepatocytes provide sufficient metabolic support for dogs to recover from otherwise lethal ischemically induced, acute liver failure.