长爪沙鼠（Meriones unguiculatus）和达乌尔黄鼠（Spermophilus dauricus）冷适应性产热机理的比较研究

【作者】 刘小团；

【导师】 孙儒泳； 李庆芬；

【作者基本信息】 北京师范大学 ， 动物生理生态学， 1998， 博士

【摘要】 褐色脂肪组织（BAT）是小型哺乳动物冷适应性产热的主要器官,其产热调控的核心因素是解偶联蛋白（UCP）。对栖息于季节变化明显、年温差较大的北方小型啮齿类而言,BAT对动物的生存尤为重要。本文选择了华北地区的野生物种——季节性冬眠的达乌尔黄鼠（Spermophilus dauricus）和非冬眠的干旱草原优势物种长爪沙鼠（Meriones unguiculatus）,比较研究了BAT产热活性和UCP基因表达的冷适应性变化。因甲状腺激素是调节哺乳动物基础代谢的重要因素并参与冷适应性产热调节,本文还探讨了两种动物甲状腺活性以及甲状腺激素在外周组织中代谢的冷适应性变化。在上述研究的基础上,我们还系统地对达乌尔黄鼠周期性冬眠和激醒过程中BAT产热调节的分子机理进行了探讨。弥补了国内外在该项工作中的不足。主要结果和结论如下: 1.常温达乌尔黄鼠和长爪沙鼠在急性和慢性冷暴露过程中,BAT重量、BAT线粒体的GTP结合能力即BAT产热活性、UCP mRNA含量以及T₄ 5′-脱碘酶的特殊活性变化趋势极其相似。表明两种动物BAT的冷诱导产热机理一致:均通过组织增生和UCP诱导性表达增强其产热活性。而且T₄ 5′-脱碘酶的激活参与了上述过程的调节。 2.与相同或相似温暖环境下的非冬眠实验啮齿类相比,长爪沙鼠BAT线粒体的嘌呤核苷酸结合水平较高。表明长爪沙鼠BAT线粒体的基础产热活性较高,具备较强NST的生理基础。这可能是长爪沙鼠适应较大日温差生境的一种策略。 3.常温达乌尔黄鼠BAT线粒体的GTP结合能力约为长爪沙鼠的两倍。表明前者BAT的基础产热活性较高,这可能与达乌尔黄鼠的冬眠特性有关。 4.达乌尔黄鼠和长爪沙鼠UCP基因的转录形式存在明显的差异。达乌尔黄鼠UCP mRNA有1.5Kb和1.9Kb两种,而长爪沙鼠UCP mRNA仅以1.5Kb的形式出现。 5.达乌尔黄鼠在周期性冬眠阵中,BAT线粒体的GTP结合能力在冬眠期虽有增更多还原

【Abstract】 Brown adipose tissue （BAT） is the major sites of cold-adaptive thermogenesis in small mammals, and uncoupling protein（UCP） in inner membrane of BAT mitochondria is the key molecule regulating and limiting thermogenesis. Thus, BAT is very important for small rodents inhabiting the North with obviously seasonal changes of climates. In this study, two species of wild rodents, one hibernator, Daurian ground squirrel （Spermophilus dauricus） and the other nonhibernator, Mongolian gerbil （Meriones unguiculatus）, inhabiting northern China have been selected, and their cold-induced thermogenesis and UCP expression of BAT have been investigated. In addition, because thyroid hormones are important factors in the regulation of basal and adaptive thermogenesis, cold-induced changes in the activity of thyroid and the metabolism of thyroid hormones in peripheral tissue have also been studied. On basis of the above, regulatory mechanism of BAT function has been probed in Daurian ground squirrel during periodical hibernation and arousal.The main results and conclusions are outlined as following:1. In Daurian ground squirrel during acute and chronic cold exposure, the process of cold-induced variations in mitochondrial GTP-binding capacity, i.e., the thermogenic activity, UCP mRNA content and T₄ 5’-deiodinase in BAT is very similar to that in Mongolian gerbil during cold acclimation. These results indicated the consistency of regulatory mechanism of cold-induced thermogenesis in BAT of the two species, including both the recruitment of BAT and the upregulation of UCP, during which the activation of T₄ 5’-deiodinase was an important regulatory factor.2. The basal GTP-binding capacity of BAT mitochondria is higher in Mongolian gerbil than that in nonhibernating laboratory rodents kept in the same or similar warm environmental temperature, indicating higher thermogenic activity of BAT which was the physiological basis of higher capacity of NST in Mongolian gerbil. It may be an adaptive strategy of Mongolian gerbil to large oscillation of daily temperature in its habitats.3. The basal GTP-binding capacity to BAT mitochondria in euthermic Daurian ground squirrel is about 2-fold that in Mongolian gerbil, indicating higher thermogenic activity of BAT in the former. It may reflect the characteristics of hibernation of Daurian ground squirrel.4. The transcriptional forms of UCP mRNA are different between Daurian ground squirrel and Mongolian gerbil, with two species of about 1 9Kb and 1.5 Kb in the former and only one of about 1 5Kb in the latter.5. In Daurian ground squirrel during periodical bouts of hibernation, UCP mRNAcontent was elevated significantly during hibernation, but the GTP-binding capacity to BAT mitochondria did not change compared with that of nonhibernating controls kept at warm temperature. When hibernating squirrels were aroused, the UCP mRNA remained the elevated level as during hibernation, but the GTP-binding capacity to BAT mitochondria increased compared with that of nonhibernating controls or hibernating ones Changes in T4 5’-deiodinase activity of BAT were similar to the variations of the UCP mRNA level, i.e., it was higher in hibernating and arousing animals than that in nonhibernating controls. These results suggest that UCP mRNA was upregulated even during hibernation, and that, similar to Mongolian gerbil and Daurian ground squirrel during cold exposure, the activation of T4 5’-deiodinase in BAT may also be an important factor for the upregulation of UCP mRNA content needed for synthesis of sufficient UCP to acquire the thermogenic capacity for arousal from hibernation. However, the factors regulating the activity of T4 5’-deiodinase may not be the same during different physiological status.6. In euthermic Daurian ground squirrel during acute and chronic cold exposure in summer, the changes in serum T3 and T4 concentrations and T4 5’-deiodinase activities of BAT and liver were similar to those in Mongolian gerbil, indicating that the cold-induced regulations of thyroid function and metabolism of thyroid hormones may be consistent in Daurian ground squirrel with Mongolian gerbil. The thyroid activity and the metabolism of thyroid hormones in peripheral tissues may be stimulated by different pathways. It led to increased T4 utilization and elevated T3 concentrations in serum and local tissues, which may take part in the regulation of basal metabolic rate and nonshivering thermogenesis.7. There are lower basal serum T3 concentration and less basal T4 5’-deiodinase activity of BAT and liver, both of which increased much more during cold exposure in Mongolian gerbil than in Daurian ground squirrel. It explained why Mongolian gerbil has a high heat and cold tolerance and can well adapt to its habitats with large oscillation of environmental temperature.8. In Daurian ground squirrel during hibernation and arousal in winter, the concentrations of serum T3 and T4 were significantly elevated, but serum T3/T4 unchanged compared with euthermic controls, which may result from either decreased the turnover of thyroid hormones or the increased thyroid activity. In euthermic Daurian squirrels kept in warm room in winter, the serum T3 and T4 concentrations were significantly higher than those in summer, suggesting that there were seasonal variations of the thyroid function or the level of thyroid hormones, and that the thyroid activity did not decrease at least prior to hibernation.更多还原