アルコール濫用による細胞・組織防御システムの破綻機構

1. 阐明乙醇通过NF-kappaB激活诱导IAP和Akt.2激活来调节细胞生存系统。在非酒精性脂肪性肝病小鼠模型中，急性乙醇治疗未引起NF-κB促炎症反应，提示脂肪性肝病存在炎症紊乱。 3．多不饱和脂肪酸会引起脂肪肝的严重炎症。然后多不饱和脂肪酸诱导肝细胞释放IL-10，从而诱导库普弗细胞活化。 4．我们建立了酒精相关猝死模型。在该模型中，TLR4信号通路在死亡原因中并未发挥重要作用。5．在脑挫裂伤模型中，预先注射乙醇会促进脑外伤后脑水肿。促进脑水肿导致死亡。乙醇注射后的脑挫裂伤不会导致促炎细胞因子的释放和细胞生存信号转录因子 NF-κB 的激活。 TBI后N-乙酰胱氨酸治疗可减轻脑水肿以维持生存。6．我们建立了类固醇诱导的股骨头坏死模型。在该模型中，TLR4信号在股骨头坏死中起着至关重要的作用。

1. It was clarified that ethanol regulates cell survival system via induction of IAP by NF-kappaB activation and activation of Akt.2. In the nonalcoholic fatty liver disease murine model, acute ethanol treatment caused no proinflammatory response via NF-kappaB, suggesting that inflammatory disturbance occurs in fatty liver disease.3. Polyunsaturated fatty acids caused sever inflammation in fatty liver. Then polyunsaturated fatty acid induced IL-10 release in hepatocytes, whichi may induce Kupffer cell activation.4. We established alcohol-related sudden death model. In this model, TLR4 signaling pathway did not play an important role in cause of death.5. In brain contusion model, prior ethanol injection promotes brain edema after traumatic brain injury. Promoting brain edema results in death. Brain contusion after ethanol injection did not cause any release in proinflammatory cytokines and activation of NF-kappaB, a cell survival signal transcription factor. N-acetyl cystine treatment after TBI reduced brain edema to keep survival.6. We established a model with steroid-induced osteonecrosis of femoral head. In this model, TLR4 signaling plays a crucial role in osteonecrosis of femoral head.