大鼠体外循环后肝脏生长激素受体mRNA的变化及其意义

Significance of the changes of growth hormone receptor mRNA in liver after cardiopulmonary bypass in a rat model

目的探讨大鼠体外循环(CPB)后肝脏生长激素受体 mRNA(GHR mRNA)的变化及意义。方法建立大鼠 CPB 模型,按照 CPB 后不同时间进行分组,检测血清生长激素(GH)、生长激素结合蛋白(GHBP)、内毒素(LPS)、白细胞介素6(IL-6)、前白蛋白(PA)水平及肝功能。RT-PCR 法检测肝组织 GHR mRNA。结果 CPB 1.0 h后肝功能损害明显,LPS、IL-6开始升高,CPB 结束后2.0h 达到峰值;GH、GHBP、GHR mRNA 变化趋势与之相反,并与黄疽程度、LPS、IL-6水平呈负相关(P<0.01)、与 PA 呈正相关(p<0.01)。结论 CPB 术后早期肝功能已受到损害,GH/GHR 轴存在明显下调,其原因可能与内毒素血症引起的生长激素受体表达受抑有关;并可进一步加重炎症反应,是介导 CPB 肝脏病理生理改变的重要因素。

Objective To study the significance of the changes of growth hormone receptor mRNA （GHR mRNA） in liver after cardiopulmonary bypass （CPB） in a rat model. Methods The rat model of CPB was established and plasma samples were collected at different intervals. Growth hormone （ GH）, GH binding protein （GHBP）, endotoxin, interleukin （IL）-6, prealbumin and liver function were determined respectively. The liver tissues were collected for the detection of the GHR mRNA by RT-PCR analysis. Results Both the lesion of liver function and the rising of the concentrations of endotoxin and IL-6 were obviously at 1 h after CPB, and increased markedly 2 h after CPB. However, the changes of concentrations of GH and GHBP,the expressions of GHR mRNA were opposite. In addition, the expression of GHR mRNA, concentrations of GH and GHBP had a significant negative correlation to the concentration of bilirubin, endotoxin respectively （ P 〈 0. 01 ）, and a positive correlation to prealbumin （P 〈 0. 01 ）. Conclusions The liver injury and downregulation of GH-GHR axis obviously exist during early stage of CPB because of the GHR mRNA expression inhibition resulting from endotoxemia. It may be one of the most important factors intervening the pathophysiology changes of liver during CPB.