Kogure K, Zhang Y Q, Shibata H, Kojima I
First Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
J Hepatol. 1998 Dec;29(6):977-84. doi: 10.1016/s0168-8278(98)80126-8.
BACKGROUND/AIM: Follistatin is an antagonist of activins and is effective in promoting liver regeneration after 70% hepatectomy. To examine its efficacy under more critical conditions, we studied the effect of follistatin on liver regeneration in 90% hepatectomized rat.
Human recombinant follistatin was infused into the portal vein immediately after 90%, hepatectomy in 24-h-starved rats, and changes in the liver regeneration rate and nuclear bromodeoxyuridine labeling were measured.
In control rats, nuclear labeling was first detected at 11 h of hepatectomy. In follistatin-treated rats, nuclear labeling was markedly increased at 3 h, and was significantly higher than that in control rats at 24, 72, 96, 120 and 144 h. The liver regeneration rate was significantly higher in follistatin-treated rats at 48, 72, 96, 120, 144 and 168 h. To determine the reason for the accelerated growth in starved rats, we compared the expression of mRNA for c-myc, p53, p21CIP1, p15INK4B, p27KIP1, and subunits of activins in fed and starved rats. mRNA for p21CIP1 and p15INK4B, but not p27KIP1 were decreased in 24 h-starved rats compared to the fed rats. mRNA for betaA subunit of activin was not detected in either fed or 24-h-starved rats, whereas that for betaC subunit was increased in starved rats.
These results indicate that follistatin induces immediate onset of DNA synthesis in 90% hepatectomized rats and is quite effective in promoting liver regeneration.
背景/目的：卵泡抑素是激活素的拮抗剂，在70%肝切除术后能有效促进肝脏再生。为了在更严峻的条件下检验其疗效，我们研究了卵泡抑素对90%肝切除大鼠肝脏再生的影响。
在24小时禁食的大鼠进行90%肝切除后，立即将人重组卵泡抑素注入门静脉，并测量肝脏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11小时首次检测到细胞核标记。在卵泡抑素处理的大鼠中，细胞核标记在3小时时显著增加，并且在24、72、96、120和144小时时显著高于对照大鼠。在48、72、96、120、144和168小时时，卵泡抑素处理的大鼠肝脏再生率显著更高。为了确定饥饿大鼠生长加速的原因，我们比较了喂食和饥饿大鼠中c-myc、p53、p21CIP1、p15INK4B、p27KIP1和激活素亚基的mRNA表达。与喂食大鼠相比，24小时饥饿大鼠中p21CIP1和p15INK4B的mRNA减少，但p27KIP1的mRNA未减少。在喂食或24小时饥饿大鼠中均未检测到激活素βA亚基的mRNA，而饥饿大鼠中βC亚基的mRNA增加。
这些结果表明，卵泡抑素可诱导90%肝切除大鼠立即开始DNA合成，并且在促进肝脏再生方面非常有效。
