Viticchi C, Moresi R, Piantanelli L
Biotechnology, Gerontological Research Department INRCA, Ancona, Italy.
Gerontology. 1999 Sep-Oct;45(5):265-8. doi: 10.1159/000022099.
Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn.
The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex.
Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The alpha(1)- and beta-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis.
Results show an increase of beta-adrenoceptor density and a decrease of alpha(1)-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly.
The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of beta-adrenoceptors, but further decreases that of alpha(1)-adrenoceptors. This differential action could be due to their differential physiological role.
先前的实验表明，将新生胸腺移植到老年受体中可恢复与年龄相关的小鼠大脑皮质肾上腺素能受体密度的下降。问题在于，在存在单一胸腺因子如胸腺调节素（TMD）的情况下是否也能获得类似结果。值得注意的是，一些胸腺因子的活性严格依赖锌（Zn），并且在补充锌的老年小鼠中，其与年龄相关的产量下降得以恢复。
上述证据促使我们验证锌和TMD单独或联合使用是否能够对小鼠大脑皮质肾上腺素能受体特性的年龄依赖性改变产生一些纠正作用。
因此，我们对四组用生理盐水、锌、TMD或锌与TMD联合处理的Balb/c小鼠进行了实验。当动物18个月大时开始处理，持续6个月。分别使用标记的哌唑嗪和碘氰吲哚洛尔通过稳态结合分析测定α(1)-和β-肾上腺素能受体特性。数据使用单因素方差分析进行分析，适当时随后进行多重比较分析。
结果显示，与生理盐水处理的对照组相比，锌处理组和锌+TMD处理组动物的β-肾上腺素能受体密度增加，α(1)-肾上腺素能受体密度降低，而受体亲和力没有显著变化。
TMD缺乏作用表明这种类型的处理不能模拟移植整个腺体的效果；不能排除不同的时间-剂量方案可能更有效。另一方面，锌处理确实调节肾上腺素能受体；然而，它对与年龄相关的β-肾上腺素能受体密度下降显示出纠正作用，但进一步降低了α(1)-肾上腺素能受体的密度。这种差异作用可能归因于它们不同的生理作用。
