Beneficial Effects of Follistatin in Hepatic Ischemia-Reperfusion Injuries in Rats

Beneficial Effects of Follistatin in Hepatic Ischemia-Reperfusion Injuries in Rats
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DOI:
10.1007/s10620-010-1401-4
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发表时间:
2011-04-01
影响因子:
3.1
通讯作者:
Arakawa, Yusuke
Arakawa, Yusuke
中科院分区:
医学3区
文献类型:
--
作者:
Kanamoto, Mami;Shimada, Mitsuo;Arakawa, Yusuke

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缺血再灌注损伤已在多种临床环境中得到证实。与肝移植和主要肝切除术相关的发病率部分是缺血再灌注损伤的结果。卵泡抑素是一种激活素结合蛋白,与激活素结合并随后阻断其作用。据报道,使用卵泡抑素阻断激活素的作用可加速缺血性肾损伤的恢复。本研究采用大鼠全肝缺血30 min再灌注模型,探讨激活素-卵泡抑素系统在肝缺血再灌注损伤中的作用。将大鼠分为两组:卵泡抑素组和对照组。在再灌注时给予卵泡抑素(1 μ g/只),这是一种激活素结合蛋白,尽管卵泡抑素组80%的动物存活,但对照组5只动物中有4只在再灌注后3天内死亡(p < 0.05)。再灌注后3 h,卵泡抑素组AST明显低于对照组(P < 0.05)。再灌注6 h时,卵泡抑素组LDH明显低于对照组(P < 0.05)。卵泡抑素抑制激活素β A亚基的mRNA表达。此外,再灌注后6 h,促滤泡素抑制素组的炎症细胞因子IL-6的表达受到抑制(p < 0.05),提示促滤泡素抑制素可降低IL-6和激活素的表达,从而对肝脏缺血再灌注损伤提供有益的支持。
Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury.Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 mu g/body), which is an activin-binding protein, was administered at the time of reperfusion.Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the beta A subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05).The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries.