近年来母亲长期高饱和脂肪酸饮食与子代神经系统发育异常日益受到关注。母亲异常代谢环境与子代脑组织炎症关系密切，而补体及其受体是联系代谢与炎症的重要桥梁之一。本课题以体外培养的野生型和C5aR-/-小鼠的小胶质细胞、星形胶质细胞和神经元为研究对象，采用生物化学、分子生物学、共聚焦显微镜等实验方法，首先评价C5a-C5aR/C5L2在脑组织炎性损伤的作用；然后检测脂肪酸干预后C5a浓度、神经细胞C5aR、C5L2表达及炎症状态变化；最后采用C5aR-/-小鼠模型，高饱和脂肪酸暴露后，检测子代血脂代谢产物和脑组织C5a浓度及炎性改变、C5aR、C5L2在神经细胞上表达及神经行为学变化，进一步明确C5a-C5aR/C5L2在高饱和脂肪酸饮食暴露后子代脑组织炎性损伤中的作用。深入研究高饱和脂肪酸饮食暴露后子代发育期脑组织炎性损伤的分子机制，有利于免疫靶向干预，并为与认知异常相关疾病发育起源提供新思路。

There is a closely relationship between mathernal high-saturated fat diet and brain inflammatory injury and cognitive problems in offspring. Saturated fatty acids can activate inflammatory and innate immune responses in the body. Many inflammatory responses in the immune system are related to the complement cleavage fragments.In the study in vitro glias and neuron are treated by C5a,C5a+ C5a antagonist , palmitic acid (PA), PA+ C5a antagonist , oleic acid(OA),OA+ C5a antagonist separatedly,then to detect the following contents:(1)the expression of Iba1,GFAP and NeuN will be tested by western blot;(2)the secretion of inflammatory factors such as TNF-α、IL-1β、IL-6、IL-10、MCP-1 will be measured by ELISA and RT-PCR;(3)the changes of p38MAPK and ERK1/2 signaling pathway;(4)the activity of cells by MTT;(5)cleaved Caspase-3 and total Caspase-3 of neurons wil be measured by western blot;(6)the concentration of C5a in the media by ELISA and the expression of C5aR and C5L2 on nerve cells by western blot and RT PCR in PA, PA+ C5a antagonist , OA,OA+ C5a antagonist groups. In the study in vivo the wild type mice and C5aR-/- mice are fed with high with saturated fat diet before mating and throughout pregnancy and laction, then to dectect the following contents in offspring (1) concentration of C5a and expression of inflammatory factors in the brain tissue;(2)the expression of C5aR and C5L2 on glias and neurons by confocal microscopy;(3)behavioral procedures by water Morris maze.Through these studies we hope we can verify the role of C5a- C5aR/C5L2 in the developing brain tissue inflammatory injury..This study explore the mechanism of developing brain tissue inflammatory injury in high-saturated-fat-diet exposed offspring.The completion of the project will help to supply the immune targeting to prevent exaggerated brain inflammation in high-fat-diet-exposed pups and a new idea to acknowledge the origion of diseases related to cognitive.