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生长激素对大鼠体外循环诱导的急性肝损伤的预防作用

The preventative role of growth hormone on acute liver injury induced by cardiopulmonary bypass in a rat model.

作者信息

An Yong, Xiao Ying-Bin

机构信息

Department of Cardiovascular Surgery, Cardiovascular Surgery Center of P.L.A, Xin-Qiao Hospital, Third Military Medical University, ChongQing 400037, China.

出版信息

Eur J Cardiothorac Surg. 2007 Jun;31(6):1037-43. doi: 10.1016/j.ejcts.2007.01.077.

Abstract

OBJECTIVE

Cardiopulmonary bypass (CPB)-induced acute liver injury is a life-threatening complication after cardiac surgery and is thought to be associated with inflammatory response and acute-phase response (APR). Recombinant human growth hormone (rhGH) can modulate the APR and inflammatory response. Here, we tested the protective effect of GH on CPB-induced liver injury in the rat.

METHODS

Adult male Sprague-Dawley rats (group G, received 2.5 mg/kg of rhGH intramuscularly at 8a.m. every 24h for 3 days and just before the initiation of CPB; group C served as control) underwent CPB (120 min, 120 ml/kg per minute, 34 degrees C) and were killed 3h after the termination of CPB.

RESULTS

Administration of rhGH markedly increased serum insulin-like growth factor (IGF)-I and IGF-I-binding protein (IGFBP)-3 compared with group C. Group G showed significantly lower serum concentrations of alanine aminotransferase and total bilirubin after CPB termination. Those receiving rhGH demonstrated a significant increase in serum prealbumin and serum transferrin and a marked decrease in serum amyloid A and serum C-reactive protein compared with group C. rhGH significantly decreased serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), whereas no changes were found for serum IL-6 and IL-10 compared with group C. rhGH significantly increased total liver protein content, hepatocyte proliferation, and decreased hepatocyte apoptosis versus group C.

CONCLUSIONS

These results suggest that GH administration in rats seems to play a preventative role in acute liver injury associated with CPB via the decrease in acute-phase proteins, proinflammatory cytokines TNF-alpha and IL-1beta, and hepatocyte apoptosis, which is associated with increase in constitutive hepatic proteins, total liver protein content, and hepatocyte proliferation.

摘要

目的

体外循环(CPB)诱发的急性肝损伤是心脏手术后一种危及生命的并发症,被认为与炎症反应和急性期反应(APR)相关。重组人生长激素(rhGH)可调节急性期反应和炎症反应。在此,我们测试了生长激素对CPB诱发的大鼠肝损伤的保护作用。

方法

成年雄性Sprague-Dawley大鼠(G组,每24小时上午8点肌肉注射2.5mg/kg rhGH,共3天,且在CPB开始前注射;C组作为对照)接受CPB(120分钟,每分钟120ml/kg,34摄氏度),并在CPB结束后3小时处死。

结果

与C组相比,rhGH给药显著增加血清胰岛素样生长因子(IGF)-I和IGF-I结合蛋白(IGFBP)-3。CPB结束后,G组血清丙氨酸转氨酶和总胆红素浓度显著降低。与C组相比,接受rhGH治疗的大鼠血清前白蛋白和血清转铁蛋白显著增加,血清淀粉样蛋白A和血清C反应蛋白显著降低。rhGH显著降低血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β),而与C组相比,血清IL-6和IL-10无变化。与C组相比,rhGH显著增加肝脏总蛋白含量、肝细胞增殖并减少肝细胞凋亡。

结论

这些结果表明,在大鼠中给予生长激素似乎通过降低急性期蛋白、促炎细胞因子TNF-α和IL-1β以及肝细胞凋亡,对与CPB相关的急性肝损伤起到预防作用,这与组成性肝蛋白、肝脏总蛋白含量增加以及肝细胞增殖有关。

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