沙棘及其有效成分对慢性疲劳综合征大鼠NK细胞功能调节的分子机制

Chronic fatigue syndrome (CFS) can interfere the function of NK cells through neuralendocrine-immune network.The main effect of Hippophae rhamnoides L. are anti-fatigue and immunoregulaiton. But the mechenism of how Hippophae rhamnoides L. works on the NK cells of CFS body need to be further researched.In the research we will establish CFS animal model with Rats.The rats will be treated with homogenate of Hippophae rhamnoides L. or total flavones of Hippophae rhamnoides L.(TFH) by intragastric administration. Then the cytotoxicity and distribution in different organs of NK cells and the related molecule will be tested. Blood serum will be detected by the weak cation exchange protein chip (WCX2) through surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and forecast the physico-chemical property and function by bioinformatics technology. The neuroendocrine mechanisms of Hippophae rhamnoides L. regulate the NK cells of CFS rats will be analyzed by detection of the main neurotransmitter，hormone and related cytokine and receptors of neurotransmitter on the surface of NK cells. The vitro experiment will also be set to study the direct effects of Hippophae rhamnoides L. on NK cells. The regulatory mechanism of Hippophae rhamnoides L. on NK cells of CFS rats will be studied based on neuralendocrine-immune network. It's great signifcance for exploitation of Hippophae rhamnoides L. production and studying the disease-causing mediation mechanism of CFS and designing intervention measures.

慢性疲劳综合征（CFS）可通过影响神经内分泌免疫网络降低NK细胞功能，沙棘具有抗疲劳、调节免疫功效。沙棘对CFS机体NK细胞功能影响及机制有待进一步研究。本项目采用CFS大鼠模型，给大鼠灌胃沙棘匀浆液或沙棘总黄酮（TFH）干预。通过检测NK细胞杀伤活性、相关分子及分布，研究沙棘及TFH对CFS机体NK细胞功能影响；采用SELDI-TOF-MS技术检测实验动物血清蛋白质指纹图谱，运用生物信息学技术对差异蛋白理化性质、功能等信息进行预测，并且通过检测血清中免疫相关主要神经递质、激素、细胞因子以及NK细胞表面相应神经递质和激素受体的表达水平，研究沙棘及TFH对CFS机体NK细胞功能调节的神经内分泌机制，结合体外实验研究其对NK细胞的直接作用及机制。基于神经内分泌免疫网络探索沙棘及TFH对CFS机体NK细胞功能调节的物质基础。这对促进沙棘产品开发、研究CFS致病的中介机制及设计干预措施有重要意义。

慢性疲劳综合征（Chronic fatigue syndrome，CFS）可以通过影响神经内分泌免疫网络降低NK细胞的功能，沙棘具有抗疲劳和免疫调节作用。本项目通过检测NK细胞杀伤活性、相关分子和分布，研究沙棘油及TFH对CFS机体NK细胞功能的影响；通过检测血清中免疫相关的主要神经递质、激素和细胞因子的表达水平，研究沙棘油对CFS机体NK细胞功能调节的神经内分泌机制，结合体外实验研究其对NK细胞的直接作用及机制。基于神经内分泌免疫网络探索沙棘油及TFH对CFS机体NK细胞功能调节的物质基础。研究结果表明，通过沙棘油灌胃干预，可明显增加CFS大鼠体重，NK细胞的杀伤活性以及在全血中的数量，上调NK细胞穿孔素与颗粒酶的表达。沙棘油可以抑制CSF大鼠血清中皮质醇、IL-1β和TNF-α，上调5-HT和IFN-γ的水平。这说明，沙棘油对CSF大鼠NK细胞功能的调节作用与其对神经内分泌功能的调节作用有关。此外，体外实验结果表明，TFH可明显促进NK92-MI细胞对K562细胞的杀伤活性，这与其促进活化受体NKP44和NKP46以及杀伤介质穿孔素和颗粒酶B表达有关。TFH可明显上调NK92-MI细胞IL-2、IL-7、IL-8、IL-15、CSF-2、CSF-3、MCP-1、MIG、IFN-γ、TNF-α、TNF-β的表达。