Kogure K, Omata W, Kanzaki M, Zhang Y Q, Yasuda H, Mine T, Kojima I
First Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Gastroenterology. 1995 Apr;108(4):1136-42. doi: 10.1016/0016-5085(95)90212-0.
BACKGROUND/AIMS: Activin A is an autocrine negative regulator of DNA synthesis in rat hepatocytes and is expressed in remnant liver after partial hepatectomy. To determine the role of activin A in liver regeneration, the effects of exogenous follistatin, which blocks the action of activin A, were examined.
Human recombinant follistatin was infused into the portal vein immediately after 70% hepatectomy. Changes in body weight, remnant liver weight, liver regeneration rate, and nuclear bromodeoxyuridine labeling were measured.
In control rats, nuclear labeling was observed at 24 hours and peaked at 36 hours after the hepatectomy. In follistatin-treated rats, nuclear labeling was first observed after 18 hours and was significantly (P < 0.05) greater than that in control rats at 24 hours. In follistatin-treated rats, both remnant liver weight and liver regeneration rate were significantly greater at 120 hours. Serum concentrations of albumin and glucose remained reduced for up to 120 hours in control rats but recovered in follistatin-treated rats.
A single administration of follistatin accelerates the initial round of DNA synthesis after partial hepatectomy. Activin A produced in remnant liver may exert tonic inhibitory effect on liver regeneration. Follistatin may be useful as a potential therapeutic agent to promote liver regeneration.
背景/目的：激活素A是大鼠肝细胞DNA合成的自分泌负调节因子，在部分肝切除术后的残肝中表达。为了确定激活素A在肝再生中的作用，研究了外源性卵泡抑素（其可阻断激活素A的作用）的效果。
在70%肝切除术后立即将重组人卵泡抑素注入门静脉。测量体重、残肝重量、肝再生率和细胞核溴脱氧尿苷标记的变化。
在对照大鼠中，肝切除术后24小时观察到细胞核标记，并在36小时达到峰值。在卵泡抑素处理的大鼠中，18小时后首次观察到细胞核标记，且在24小时时显著高于对照大鼠（P<0.05）。在卵泡抑素处理的大鼠中，120小时时残肝重量和肝再生率均显著更高。对照大鼠血清白蛋白和葡萄糖浓度在长达120小时内持续降低，但在卵泡抑素处理的大鼠中恢复。
单次给予卵泡抑素可加速部分肝切除术后第一轮DNA合成。残肝中产生的激活素A可能对肝再生产生持续性抑制作用。卵泡抑素可能作为促进肝再生的潜在治疗药物。
