TLR4拮抗剂减轻小鼠脑出血的炎症损伤及机制-神经病学专业论文.docxVIP

第三军医大学硕士学位论文 第三军医大学硕士学位论文 PAGE PAGE 10 TUNEL Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling 原位末端标记法 WB Western blot 免疫蛋白质印迹 WT Wild type 野生型 Toll-like Receptor 4 antagonist attenuates intracerebral hemorrhage-induced brain injury and the mechanism* Abstract Intrcerebral hemorrhage (ICH) is a common type of fatal stroke, accounting for about 20% to 30% of all strokes, and this will be higher in China. As Chinese aging society is coming and changing of living style, more and more patients suffered from obesity, hypertension, diabete will consiquently lead to higher incidence of ICH. Hemorrhagic strokes are associated with high mortality and morbidity, its mortality rates of 60-80 per million and its morbidity reaches to 30% to 40%. 70% to 80% survivors lose their labor and have disabilities, which raises a burden for their families and society. Increasing evidence shows that innate immune responses and inflammatory injury play a critical role in ICH-induced neurological deficits. However, the signaling pathways involved in ICH-induced inflammatory responses remain elusive. Toll-like receptor 4 (TLR4) belongs to a large family of pattern recognition receptors (PRRs) which has 11 members in human. They play a key role in innate immunity and inflammatory responses. Researchs revealed that TLR4 plays an important role in inflammatory injury in Alzheimer’s disease (AD), intrecerebral ischemia, Parkinson disease (PD) etc. Our latest research demonstrated the involvement of TLR4 signaling in inflammatory responses causeed secondary injury after ICH. We found that TLR4 contribure to poor outcome after intracerebral hemorrhage. That prompted the potential for therapeutic intervention by targeting TLR4 signaling. In this study, we explored the protective effect of TLR4 antagonist on mice after ICH. The ICH model was established by injection of autologous non-anticoagulated blood into the caudate nucleus. TAK242 was intraperitoneally injected 6 h after IC