黑线仓鼠Kiss-1/GPR54系统表达与免疫能力之间的生理权衡机制

Trade-off is the key idea of life history theory. The mechanism of physiological trade-off between current reproduction and immune function faciliating future reproduction in animals has been a focus in ecoimmunology all along. Striped hamsters (Cricetulus barabensis) which distribute mainly in northern China are primary agricultural pest rodents. Their reproductive activities demonstrate evident seasonal variation, hence striped hamsters are good model systems to investigate the mechanism of physiological trade-off between reproduction and immune responses. By using molecular biological and immunological methods, we will examine seasonal changes of the expression of Kiss-1/GPR54 (G protein-coupled receptor 54) and the immunological parameters such as innate, humoral and cellular immunity, cytokines in striped hamsters in the field in order to identify their relationship in different seasons. By simulating the stressful conditions in winter (low temperature and food shortage), we are to elucidate how the expression of Kiss-1/GPR54 trade-off immune funciton under the stress of energy deficiency. Our hypothesis that leptin and testosterone underlie the trade-off between the expression of Kiss-1/GPR54 and immune funciton will be testified by removing partial white adipose tissues, testis and supplementing leptin and testosterone, respectively. At the same time, the immunocompetence handicap hypothesis will be testified. Our findings will unravel the mechanism of physiological trade-off between current and future reproduction in small mammals from the perspective of ecoimmunology, which will deepen our understanding of the characteristics of seasonal reproduction and their adaptive strategies to the enviroments. Meanwhile the development of ecoimmunology will be also boosted.

权衡是生活史理论的核心，动物当前繁殖与有利于未来繁殖的免疫能力之间权衡的生理机制问题，是生态免疫学关注的焦点。黑线仓鼠是分布于我国北方的重要农业害鼠，繁殖活动具有明显的季节性，是研究繁殖与免疫之间权衡机制的好模型。我们通过采用分子生物学和免疫学方法，对野外黑线仓鼠Kiss-1/GPR54系统表达和天然免疫、体液免疫、细胞免疫、细胞因子等免疫指标的季节性变化进行测定，确定它们在不同季节时的权衡关系；通过实验室内模拟冬季环境 (低温和食物缺乏)，明确在能量缺乏应激时，Kiss-1/GPR54系统表达与免疫能力之间如何权衡，通过切除部分脂肪和睾丸以及补充瘦素和睾酮的实验，验证瘦素和睾酮介导了黑线仓鼠Kiss-1/GPR54表达与免疫能力之间权衡的假说，同时对免疫功能障碍假说进行检验。研究结果将从生态免疫学视角揭示动物繁殖与免疫之间的生理权衡机制，深化对动物季节性繁殖的认识，促进生态免疫学的发展。

动物繁殖与反映生存能力的免疫之间是否存在权衡是生态免疫学关注的核心问题，本项目以主要分布于我国北方的重要农业害鼠黑线仓鼠为研究对象，开展了以下方面的研究：通过检测不同季节黑线仓鼠Kiss-1/GPR54表达和免疫能力，以期获得在不同季节繁殖相关基因表达与免疫间的关系，通过室内模拟冬季应激环境 (低温和食物缺乏)，探讨在能量缺乏应激时，Kiss-1/GPR54表达与免疫之间的关系；通过切除部分脂肪和补充瘦素的实验，探讨瘦素是否介导了黑线仓鼠Kiss-1/GPR54表达与免疫能力之间的权衡；通过切除睾丸与补充睾酮的实验，探索了性激素在免疫中的作用；通过检测渐变高低温条件下Kiss-1/GPR54表达和免疫能力，以期了解高低温如何影响Kiss-1/GPR54表达与免疫间的关系。我们发现黑线仓鼠Kiss1、GnRH与GPR54的基因表达与季节、性别以及所检测的器官组织包括下丘脑、性腺（雄性为睾丸、附睾与储精囊，雌性为卵巢与子宫）有关，免疫学指标包括天然免疫、细胞免疫、体液免疫、细胞因子和血液学指标也表现出不同的季节变化，一些繁殖相关基因表达与免疫指标呈显著负相关，暗示动物繁殖与免疫能力之间可能存在着权衡。通过模拟冬季能量缺乏应激条件，发现低温与限食对Kiss1、GnRH、GRP5表达影响不同，并且具有组织器官特异性，低温与限食对免疫指标和激素（瘦素、雌二醇、皮质酮）水平的影响存在差异。切除脂肪后黑线仓鼠繁殖功能相关基因表达水平下降，而补充瘦素后，其表达水平升高，暗示能量贮存降低对Kiss1/GPR54基因表达的抑制作用可能是由瘦素介导的。脂肪切除降低了细胞和体液免疫，而补充瘦素后细胞与体液免疫增加，表明瘦素可能介导了脂肪含量降低对细胞和体液免疫的抑制作用。补充睾酮抑制小鼠的细胞免疫功能，支持免疫功能障碍假说，但对天然和体液免疫没有影响，则不支持该假说。黑线仓鼠下丘脑、卵巢和子宫中KiSS-1、GnRH和GPR54基因的表达均不受渐变高低温的影响，不同免疫指标与激素对高低温的响应存在差异。这些研究结果初步揭示了动物繁殖与免疫之间权衡的生理机制，使我们能更深入地理解动物适应环境的策略。