Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
Mech Ageing Dev. 2011 Mar;132(3):103-9. doi: 10.1016/j.mad.2011.01.002. Epub 2011 Feb 1.
Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.
热量限制（CR）通过抑制生长激素（GH）/胰岛素样生长因子 1 轴（IGF-1）发挥抗衰老作用。本研究探讨了适度抑制 GH 信号对应激反应的影响，并将其与 CR 的影响进行了比较。使用了一种转基因雄性大鼠的杂合子（tg/-）大鼠和野生型（WT）大鼠，该大鼠通过反义 GH 基因的过表达抑制 GH 信号。大鼠从 6 周龄起自由进食（AL）或 30%CR 饮食。在 6 个月大时，在 LPS 注射后 0 至 8 小时之间处死大鼠，以评估急性应激反应。与 WT 大鼠相比，tg/-大鼠的组织损伤较少，表现为血液天冬氨酸转氨酶（AST）浓度降低。tg/-大鼠的血浆 TNF-α、IL-6 和干扰素（IFN）-γ水平也呈递增性波动，且减轻程度更大。tg/-大鼠中 NF-κB（一种氧化还原敏感的转录因子）的激活略有减弱，而 AP-1 活性增加。在 CR 组与 AL 组相比，也观察到了类似的趋势。本研究结果表明，GH/IGF-1 轴参与了 CR 对应激反应的影响，即使 CR 并非仅通过 GH 轴起作用。
