老年大鼠下丘脑-垂体-肾上腺-胸腺轴基因表达谱的研究

Study of the gene expression profile of hypothalamus-pituitary-adrenal-thymus axis in aged rats

目的 阐明衰老时下丘脑 -垂体 -肾上腺 -胸腺 (HPAT)轴基因表达规律 ,探索神经内分泌和免疫衰老的分子机制。方法 利用基因芯片技术研究老年大鼠与青年大鼠 HPAT轴差异表达的基因。结果 老年大鼠下丘脑多种神经递质或其受体如 GABA- AR、α1 ER、Glu R、多巴胺转运蛋白表达下调 ;垂体多种促性腺激素包括 FSH、LH、Gn RH下调 ;生长激素和生长激素释放因子受体下调 ;脾淋巴细胞促凋亡基因 caspase- 1、caspase- 3、CPP32β、Dnaseγ、PKC delta、Bnip31、p47上调 ,抗凋亡基因 cathepsin B、MTA1下调 ,抗增殖基因 Rb、BTG1表达上调 ,促增殖基因 Jagged1及 c- myc、c- fos、v- jun、Rgc32、Cyclin B1、Cyclin G- associated kinase下调。结论 衰老时 HPAT轴的衰退以下丘脑 -垂体 -性腺轴、下丘脑 -垂体 -生长激素轴、免疫系统受损最为明显 ,神经递质、生长激素、促性腺激素基因低表达及免疫细胞促凋亡基因高表达而抗凋亡基因低表达 ,促增殖基因低表达而抗增殖基因高表达是受损的分子机制。

Objective To investigate the gene expression profile of hypothalamus-pituitary-adrenal-thymus (HPAT) axis in aged rats and study the molecular mechanism of neurocrine and immunity senescence. Methods Differential gene expression of HPAT from 26-month-old rats or 7- month-old rats was studied with gene chip technology. Results Compared with young rats, the expression of those genes was down-regulated including several neurotransmitter and its receptors such as GABA-AR,α 1 ER, Glu R, dopamine transporter, several gonadotropid hormone such as FSH, LH, GnRH, growth hormone and growth hormone releasing factor receptors, apopotosis-inhibiting genes including Cathepsin B, MTA1 and proliferation-promoting genes including Jagged1, c-myc, c-fos, v-jun, Rgc32, Cyclin B1, Cyclin G-associated kinase. Meanwhile, in lymphocytes, the expression of apoptosis-promoting genes including Caspase1, Caspase2,CPP32β, Dnaseγ, PKC delta, Bnip31, p47 was lower in aged rats. Conclusions Hypothalamus-pituitary-gonad axis, hypothalamus-pituitary-growth hormone axis and immune system are most seriously damaged when aging. The lower expression of related genes such as neurotransmitter receptor genes, GH gene and gonadotropic hormone genes and the unbalance of the apoptosis-related and proliferation-related genes in immunocytes are the important molecular mechanisms of this damage.