Trejo-Solís Cristina, Chagoya De Sánchez Victoria, Aranda-Fraustro Alberto, Sánchez-Sevilla Lourdes, Gómez-Ruíz Celedonio, Hernández-Muñoz Rolando
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico.
Lab Invest. 2003 Nov;83(11):1669-79. doi: 10.1097/01.lab.0000095688.89364.bf.
We have proposed that controlled peroxidative modifications of membranes could be playing a role in the early steps of liver regeneration. Hence, lipid peroxidation (LP) was modified in vivo by treatment with vitamin E in rats subjected to partial hepatectomy (PH), and its influence on liver regeneration was evaluated. Our results, using several methods to monitor LP, indicate that vitamin E administration promoted a decreased LP rate in liver subcellular membranes. Vitamin E drastically diminished cytosolic LP, shifting earlier increased LP in plasma membranes, and promoted a higher increase of nuclear LP in animals subjected to PH. Pretreatment with vitamin E induced a striking reduction of liver mass recovery and nuclear bromodeoxyuridine labeling (clearly shown at 24 hours after surgery), as well as promoted a decreased expression of cyclin D1 and of the proliferating cell nuclear antigen after PH. These effects seem to lead to a decreased mitotic index at 48 hours after PH. Vitamin E pretreatment also diminished PH-induced hypoglycemia but elevated serum bilirubin level, which was not observed in PH animals without vitamin treatment. In conclusion, an enhanced but controlled LP seems to play a critical role during the early phases of liver regeneration. Decreasing magnitude or time course of the PH-promoted enhanced LP (at early post-PH stages) by in vivo treatment with vitamin E could promote an early termination of preparative cell events, which lead to the replicative phase, during PH-promoted liver proliferation. The latter could have a significant implication in the antitumorigenic effect ascribed to the treatment with vitamin E.
我们曾提出，膜的可控过氧化修饰可能在肝脏再生的早期步骤中发挥作用。因此，我们通过给部分肝切除（PH）的大鼠注射维生素E来在体内改变脂质过氧化（LP），并评估其对肝脏再生的影响。我们使用多种方法监测LP的结果表明，给予维生素E可使肝脏亚细胞膜中的LP速率降低。维生素E显著降低了胞质LP，使质膜中先前升高的LP发生改变，并促使PH大鼠的核LP有更高的增加。维生素E预处理导致肝脏质量恢复和核溴脱氧尿苷标记显著降低（在手术后24小时明显可见），并促使PH后细胞周期蛋白D1和增殖细胞核抗原的表达降低。这些作用似乎导致PH后48小时有丝分裂指数降低。维生素E预处理还减轻了PH诱导的低血糖，但升高了血清胆红素水平，而在未接受维生素治疗的PH动物中未观察到这种情况。总之，增强但可控的LP似乎在肝脏再生的早期阶段起关键作用。通过体内给予维生素E降低PH促进的增强LP（在PH后早期阶段）的幅度或时间进程，可能会促进准备性细胞事件的早期终止，这些事件会导致在PH促进的肝脏增殖过程中进入复制阶段。后者可能对归因于维生素E治疗的抗肿瘤作用有重要意义。
