Masson S, Scotté M, Garnier S, François A, Hiron M, Ténière P, Fallu J, Salier J P, Daveau M
INSERM Unit 519, Rouen-France and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen-France.
Apoptosis. 2000 Apr;5(2):173-9. doi: 10.1023/a:1009645015601.
Liver regeneration after partial hepatectomy or liver injury is controlled by a wide variety of growth factors that are proven activators or inhibitors of hepatocyte proliferation. Liver regeneration post-hepatectomy has been proven to be decreased and delayed in cirrhotic vs. normal liver. Apoptosis seems to play an important role in cellular proliferation and in liver regeneration. Therefore, this study has analyzed the expression of apoptosis-associated genes following 2/3 hepatectomy in cirrhotic vs. normal rats. Cirrhosis was induced by a weekly intragastric administration of CCl4 for 16 weeks followed by hepatectomy and histological examination of the resected liver. Rats were sacrificed at 6 h, 12 h, 24 h, or 72 h after liver resection. The expression of proapoptotic (Bad, Bak, Bax) and antiapoptotic (Bcl-2, Bcl-XL) genes was analyzed by quantitative RT-PCR. We have observed an early increase in antiapoptotic mRNA levels and a delayed increase in proapoptotic mRNA levels in normal liver following hepatectomy. Before resection, proapoptotic mRNA levels were significantly higher in cirrhotic vs. normal liver. After hepatectomy, apoptotic mRNA levels were decreased and delayed as compared with that observed following hepatectomy in normal liver. These results indicate that apoptosis takes place in liver during CCl4-induced cirrhosis and could participate in the impaired regenerative response observed in cirrhotic liver.
部分肝切除或肝损伤后的肝脏再生受多种生长因子调控，这些生长因子已被证实是肝细胞增殖的激活剂或抑制剂。与正常肝脏相比，肝硬化肝脏在肝切除术后的再生已被证明会减少和延迟。细胞凋亡似乎在细胞增殖和肝脏再生中起重要作用。因此，本研究分析了肝硬化大鼠和正常大鼠在2/3肝切除术后凋亡相关基因的表达。通过每周一次胃内注射四氯化碳，持续16周诱导肝硬化，随后进行肝切除并对切除的肝脏进行组织学检查。在肝切除术后6小时、12小时、24小时或72小时处死大鼠。通过定量逆转录聚合酶链反应分析促凋亡基因（Bad、Bak、Bax）和抗凋亡基因（Bcl-2、Bcl-XL）的表达。我们观察到，正常肝脏在肝切除术后抗凋亡mRNA水平早期升高，促凋亡mRNA水平延迟升高。在切除前，肝硬化肝脏中促凋亡mRNA水平显著高于正常肝脏。肝切除术后，与正常肝脏肝切除术后观察到的情况相比，凋亡mRNA水平降低且延迟。这些结果表明，在四氯化碳诱导的肝硬化过程中肝脏发生了细胞凋亡，并且可能参与了肝硬化肝脏中观察到的再生反应受损。
