高脂喂养肥胖大鼠下丘脑及肝脏内细胞因子信号转导抑制物－3 mRNA表达的研究

doi:10.3877/cma.j.issn.1673-5250.2008.03.104

目的

瘦素抵抗被认为是儿童肥胖症的主要发病机制。细胞因子信号转导抑制物－3(suppressors－of－cytokine－signaling 3, SOCS3)作为瘦素受体后Janus蛋白激酶－信号转导及转录激活蛋白(JAK－STAT)信号传导通路的主要负性调节因子，可能参与瘦素抵抗的发生。本研究从瘦素受体基因表达和瘦素受体后Janus蛋白激酶－信号转录及转录激活蛋白传导通路水平，研究瘦素抵抗的可能发生机制。

方法

以高脂饮食制备幼年、雄性肥胖大鼠模型，利用半定量RT－PCR法检测肥胖大鼠下丘脑及肝脏组织内中细胞因子信号转导抑制物－3 mRNA、瘦素长型受体(OB－Rb)mRNA表达的改变，探讨细胞因子信号转导抑制物－3 mRNA表达与高瘦素血症及与瘦素长型受体mRNA表达的关系。

结果

与对照组相比，肥胖大鼠下丘脑及肝脏内，细胞因子信号转导抑制物－3表达升高(P<0.01)，并与血清瘦素水平呈正相关(r＝0.666，r＝0.790，P<0.01)。肥胖组大鼠下丘脑及肝脏内，细胞因子信号转导抑制物－3 mRNA(相对灰度值)与瘦素长型受体mRNA水平呈显著负相关(r＝－0.526，r＝－0.585，P<0.05)。

结论

肥胖大鼠中枢及外周组织的细胞因子信号转导抑制物－3表达上调，使瘦素受体后JAK－STAT信号转导通路抑制，可能参与了瘦素抵抗的发生机制。

关键词: 肥胖, 瘦素抵抗, 瘦素受体, 细胞因子信号转导抑制物－3

Objective

Leptin resistance is thought to be a main mechanism of child obesity. Suppressors-of-cytokine-signaling 3 (SOCS3) is a leptin inducible inhibitor of leptin signaling and a potential mediator of leptin resistance in obesity. From the aspect of expression in OB-Rb mRNA and post-receptor signal transduction pathway, we tried to probe the possible pathogenesis of leptin resistance.

Methods

4-week-old healthy male SD rats were fed with high-fat diet to set up the animal model of dietary obesity. Expressions of suppressors-of-cytokine-signaling 3 mRNA, OB-Rb mRNA in the hypothalamus and liver were detected with semi-quantitative RT-PCR. And the relationship between the expression of suppressors-of-cytokine-signaling 3 mRNA and serum leptin levels, between the expression of suppressors-of-cytokine-signaling 3 mRNA and OB-Rb mRNA were analyzed respectively.

Results

Compared with the control group, serum leptin levels were elevated obviously in the obese rat group (P<0.01), and the expression of suppressors-of-cytokine-signaling 3 mRNA in hypothalamus and liver were also increased remarkebly (P<0.01, respectively), and there was a significant positive correlation between serum leptin concentration and the suppressors-of-cytokine-signaling 3 mRNA level in the obese rat group (r=0.666, r=0.790, P<0.01, respectively). On the contrary, there were negative relationships between the expression of suppressors-of-cytokine-signaling 3 mRNA and OB-Rb mRNA in hypothalamus and liver (r=-0.526, r=-0.585, P<0.01, respectively).

Conclusion

To up-regulate the expression of suppressors-of-cytokine-signaling 3 mRNA may be related to leptin resistance in obese rats.

Key words: obesity, leptin resistance, leptin receptor, suppressors-of-cytokine-signaling 3(SOCS3)

图1　高脂饲养与普通饲料喂养SD大鼠的体重变化

图2　下丘脑及肝脏组织中SOCS3 mRNA RT－PCR产物电泳图

图3　下丘脑及肝脏组织中OB－Rb mRNA RT－PCR产物电泳图

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Study on the Expression of Suppressors-of-Cytokine-Signaling 3 mRNA in Hypothalamus and Liver in Obese Rats Fed With High-Fat Diet

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Study on the Expression of Suppressors-of-Cytokine-Signaling 3 mRNA in Hypothalamus and Liver in Obese Rats Fed With High-Fat Diet