下丘脑神经生长因子前体对心肺转流大鼠室旁核场电位的影响

Effect of hypothalamic nerve growth factor precursor on field potential of paraventrucular nucleus during rat cardiopulmonary bypass

目的探讨下丘脑神经生长因子前体(nerve growth factor precursor, proNGF)在大鼠心肺转流(CPB)过程中的改变以及可能对交感输出产生的作用。方法雄性SD大鼠42只,3～4月龄,体重350～500 g。其中18只建立大鼠CPB模型,将大鼠分为三组:对照组、CPB组和心肌缺血-再灌注组(IR组)。CPB 110 min后,取大鼠下丘脑和心脏节段背根神经节,检测NGF mRNA表达量以及proNGF蛋白含量。另选取12只大鼠双侧室旁核(PVN)插管,连续7 d注入proNGF蛋白,检测并记录延髓头端腹外侧区(RVLM)场电位。另选取12只大鼠侧脑室注入proNGF蛋白,检测并记录给药前后PVN场电位;PVN场电位记录结束后,检测下丘脑谷氨酸以及γ-氨基丁酸(GABA)含量。结果与对照组比较,CPB末CPB组、IR组proNGF蛋白含量明显升高(P<0.05),DRG以及下丘脑NGF mRNA表达量明显升高(P<0.05)。注入proNGF蛋白后,RVLM以及PVN场电位1～4 Hz频段能量明显下降,其余频段能量明显升高(P<0.05);侧脑室注入proNGF对下丘脑谷氨酸无明显影响,但明显降低GABA含量(P<0.05)。结论大鼠CPB后下丘脑proNGF表达增加,可能参与下丘脑交感输出改变。

Objective To evaluate the effect of cardiopulmonary bypass(CPB)on the expression of hypothalamic nerve growth factor precursor(proNGF)and the influence of hypothalamic proNGF on the sympathetic output of paraventrucular nucleus.Methods Forty-two male SD rats,aged 3-4 months,weighing 350-500 g,were divided into control group,CPB group and ischemia reperfusion(IR)group.At the end of CPB for 110 min,hypothalamus and dorsal root ganglion(DRG)were taken to measure the levels of proNGF mRNA and hypothalamic proNGF protein.Mini pipe was put into bilateral paraventrucular nucleus(PVN)and human recombination proNGF protein was injected into PVN for 7 d before the local field potentials(LFP)of RVLM was recoreded.Human recombination proNGF protein was administrated into lateral ventricle,the prior-administration-LFP of PVN and post-administration-LFP were recorded and compared.At the end of the experiment,hypothalamus was taken to measure the levels of glutamate and gammer amino butyric acid(GABA).Results Hypothalamic proNGF protein in CPB group and IR group was higher than that in the control group(P<0.05);NGF mRNA of hypothalamus and DRG in CPB and IR group were higher than those of control group(P<0.05).In PVN and RVLM,after the administration of proNGF protein,the power of delta band significantly decreased and other bands increased(P<0.05).The hypothalamic GABA level decreased(P<0.05)with no change of hypothalamic glutamate after proNGF was injected into lateral ventricle.Conclusion CPB increases the expression of proNGF in the hypothalamus contributing to the changes of hypothalamic sympathetic output.