Ghrelin对雌激素诱导雄性小鼠胸腺萎缩的逆转作用及其部分细胞因子基因表达的变化
he reverse effects of exogenous ghrelin on estrogen-induced thymic atrophy and the changes of several thymic cytokine gene expressions in male mouse
目的：深入探讨Ghrelin对雌激素诱导雄性小鼠胸腺萎缩的逆转作用及其分子机制。方法：SPF级6周龄Balb/c雄性小鼠60只，随机分为3组，每组20只，适应饲养1周后进行动物试验：雌激素+Ghrelin实验组：前两周隔日腹腔注射苯甲酸雌二醇注射液（含苯甲酸雌二醇0.1mg）0.05 mL /只，后2周按每日腹腔注射Ghrelin（含Ghrelin 60μg） 0.1 mL /只；雌激素+生理盐水对照组：前两周隔日腹腔注射苯甲酸雌二醇注射液（含苯甲酸雌二醇0.1mg）0.05 mL /只，后2周按每日腹腔注射0.9%生理盐水0.1mL/只；生理盐水对照组：前2周按0.05mL/只隔日腹腔注射0.9%生理盐水，后2周按0.1mL/只每日腹腔注射0.9%生理盐水。动物实验结束后，统计小鼠胸腺指数，应用光镜观察胸腺形态学变化，采用实时荧光定量PCR法检测胸腺中12种细胞因子mRNA表达量的变化。结果：注射Ghrelin后，雌二醇诱导的小鼠萎缩胸腺在形态学上基本恢复到正常水平，胸腺中白细胞介素1（IL-1）、IL-2、IL-4、IL-6、IL-12、干扰素（IFN-γ）、白血病抑制因子（LIF）、抑瘤素（OSM）、干细胞因子（SCF）、胸腺体液因子（THF）、肿瘤坏死因子（TNF-α） mRNA含量显著降低（P<0.05）， 而IL-7 mRNA含量稍微升高（P>0.05）。结论：Ghrelin对雌激素诱导的小鼠胸腺萎缩具有逆转作用，其机制可能是：一方面通过抑制IL-6、OSM、LIF、SCF等细胞因子的表达，从而促进胸腺细胞的增殖；另一方面通过抑制IL-1、IL-2、IL-4、IL-12、THF等细胞因子的表达，从而减少TNF-α和IFN-γ的分泌，进而抑制胸腺细胞的凋亡。
Objective: We aim to deeply investigate the reverse effects and its mechanisms of ghrelin on estrogen-induced thymus atrophy in male mouse. Methods: we chose 60 6-weeks-old SPF Balb/c male mice, randomly divided them into three groups, with 20 in each group. After raising for a week, we started the animal tests: Estrogen+ghrelin experimental group: the mice in the group were intraperitoneally injected with estradiol benzoate (0.05mL/0.1mg) every other day for two weeks, the late two weeks were administrated with ghrelin (0.1mL/120μg) in the same way; Estrogen+saline control group: the mice in the group were intraperitoneally injected with estradiol benzoate (0.05mL/0.1mg) every other day for two weeks, the late two weeks were administrated with 0.9% physiological saline (0.1mL per mouse) in the same way; Saline control group: the mice in the group were intraperitoneally injected with 0.9% physiological saline (0.05mL per mouse) every other day for two weeks, the late two weeks were administrated with 0.9% physiological saline (0.1mL per mouse) in the same way. After the animal tests, we calculated the thymus index and observed the morphology of thymus by light microscope and detected the mRNA expression levels of 12 thymic cytokines by real-time PCR. Results: After administration with ghrelin, the estradiol-induced atrophic thymus almost returned to normal in morphology, and the expression levels of interleukin (IL)-1, I-2, IL-4, IL-6, IL-12, interferon (IFN)-γ, leukemia inhibitory factor (LIF), oncostatin M (OSM), stem cell factor (SCF), thymus humoral factor (THF), tumor necrosis factor (TNF)-α mRNA in thymus were significantly decreased(P<0.05), while IL-7 slightly increased(P>0.05). Conclusion: The results revealed that there possibly are two mechanisms to reverse estrogen-induced mouse thymus atrophy by ghrelin. On the one hand, the thymocyte proliferation was promoted by inhibiting the expression of IL-6, OSM, LIF, SCF etc. On the other hand, the expressions of TNF-α and IFN-γ were reduced by decreasing the production of IL-1, IL-2, IL-4, IL-12 etc, which inhibited thymocyte apoptosis.
马勇江、张媛、李玉谷、邓海英、刘健红、叶亚琼、尹帆、李英
基础医学生理学分子生物学
Ghrelin雌二醇细胞因子胸腺小鼠
GhrelinEstradiolCytokinesThymusMouse
马勇江,张媛,李玉谷,邓海英,刘健红,叶亚琼,尹帆,李英.Ghrelin对雌激素诱导雄性小鼠胸腺萎缩的逆转作用及其部分细胞因子基因表达的变化[EB/OL].(2012-12-17)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201212-366.点此复制
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