心力衰竭大鼠脑脊液及血清瘦素改变的研究

Cerebrospinal Fluid and Serum Leptin Levels in Rats with Heart Failure

【目的】检测心力衰竭大鼠血清、脑脊液瘦素水平及脑脊液/血清瘦素比值改变,对心衰大鼠的瘦素水平、瘦素抵抗及瘦素在血-脑脊液处的转运进行初步探讨。【方法】通过缩窄雄性Wistar大鼠腹主动脉制成心力衰竭模型。30只大鼠随机分成空白对照组、假手术对照组和心衰组。预实验应用超声心动图和血流动力学检测证实术后4个月大鼠已经出现明显心衰。术后4个月采集脑脊液、血清,ELISA法测定瘦素水平。【结果】心衰组的血清瘦素水平较假手术及空白对照组明显升高[(8.1±4.0)ng/mLvs(3.7±1.7)ng/mL,(3.1±1.4)ng/mL,P<0.01]。3组脑脊液瘦素水平无显著差异。心衰组脑脊液/血清瘦素比值较两对照组明显降低(10±7vs18±8,22±12,P<0.01)。两对照组血清瘦素水平及脑脊液/血清瘦素比值无显著差异。对照组脑脊液瘦素与血清瘦素呈正相关(r=0.724,P<0.05),心衰组两者相关性消失。【结论】心衰大鼠血清瘦素水平升高,脑脊液瘦素水平无显著改变,脑脊液/血清瘦素比值下降,脑脊液瘦素与血清瘦素相关性减弱。支持瘦素血-脑脊液饱和转运系统的存在,提示瘦素进入中枢系统的转运障碍是瘦素抵抗的一个重要原因。

[Objective] To investigate the leptin level, letpin resistance and leptin transport at blood-cerebral barrier in the rats with heart failure through assaying cerebrospinal fluid （CSF） and serum leptin level and CSF/ serum leptin ratio. [Methods ] Thirty male Wistar rats were randomly divided into blank control group （BC）, pseudo-operation control group （OC） and heart failure group （HF） after heart failure was induced by constricting abdominal aorta for 16 weeks. Leptin level of serum and CSF were determined by ELISA. [Results] Serum level of lepin was increased in HF group compared to BC and OC groups[（8.1 ± 4.0） ng/mL vs （3.7 ± 1.7） ng/mL, （3.1 ± 1.4） ng/mL,P〈 0.01]. There was no significant difference of CSF leptin level among three groups. CSF/serum ratio was significantly decreased in HF group compared to BC and OC groups（ 10 ± 7 vs 18 ± 8, 22 ± 12, P〈 0.01 ）. No significant difference of serum leptin level and CSF/serum ratio was found between two control groups. CSF leptin level correlated positively with serum leptin level （r=0.724, P〈 0.05）in BC and OC groups and the relationship disappeared with increased serum leptin level in HF group. [Conclusions] Serum level was increased in the rats with heart failure while there was no significant change of CSF leptin level. Decreased CSF/serum leptin ratio and weakend correlation between CSF and serum leptin level indicates the existence of saturable leptin blood-CSF transport system and that deteriorating letpin transport from peripheral blood to CSF is one possible reason for letpin resistance.