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

酗酒导致细胞和组织防御系统崩溃的机制

• 批准号: 18390206
• 负责人: MATSUMOTO Hiroshi
• 金额: $ 10.27万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390206/
• 关键词: alcohol; cell survival; NAFLD; osteonecrosis of femoral head; brain contusion; innate immunity; polyunsaturated fatty acid; 肝障害

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.

1.已阐明乙醇通过NF-κ B活化和Akt活化诱导IAP来调节细胞存活系统。在非酒精性脂肪性肝病小鼠模型中，急性乙醇处理没有引起通过NF-κ B的促炎症反应，提示脂肪性肝病中存在炎症紊乱.多不饱和脂肪酸引起脂肪肝严重炎症。多不饱和脂肪酸可诱导肝细胞释放IL-10，从而激活枯否细胞.建立酒精性猝死模型。在该模型中，TLR 4信号通路在死亡原因中没有发挥重要作用.在脑挫伤模型中，预先注射乙醇可促进创伤性脑损伤后的脑水肿。促进脑水肿导致死亡。乙醇注射后的脑挫伤没有引起任何促炎细胞因子的释放和细胞存活信号转录因子NF-κ B的激活。N-乙酰胱氨酸治疗可减轻脑水肿，维持生存.建立激素性股骨头坏死模型。在该模型中，TLR 4信号传导在股骨头坏死中起着至关重要的作用。

项目成果

Saturated and monounsaturated fatty acids increase interleukin-10 production in rat hepatocytes.

饱和和单不饱和脂肪酸可增加大鼠肝细胞中白细胞介素 10 的产生。

• 发表时间: 2007
• 期刊: Jpn.J.Alcohol ＆ Drug Dependence 42 ・1
• 作者: 森田恭子;関山敦生;六反一仁;Nishitani Y
• 通讯作者: Nishitani Y

Acute ethanol induces activation of Akt and NFkappaB to prevent activation of JNK, a cell death protein kinase, in the liver

急性乙醇诱导 Akt 和 NFkappaB 激活，以防止肝脏中 JNK（一种细胞死亡蛋白激酶）的激活

• 发表时间: 2006
• 作者: Matsumoto H;Nishitani Y;Okazaki S;Fujii K;Umetani K;Imabayashi K;Yajima H;Katada R.
• 通讯作者: Katada R.

Ethanol expands life span? : an experimet with the nematode Caenorhabditis elegans

乙醇可以延长寿命吗？

• 发表时间: 2006
• 作者: Matsumoto H;Yamamoto K;Yajima H.
• 通讯作者: Yajima H.

Effects of ethanol on brain contusion.

乙醇对脑挫裂伤的影响。

• 发表时间: 2007
• 期刊: Alcohol Biomed Res 27
• 作者: Katada R;Nishitani Y;Okazaki S;Yajima H;Imabayashi K;Matsumoto H
• 通讯作者: Matsumoto H

Role of PGC-1alpha in development of non-alcoholic fatty liver disease in mice

PGC-1α 在小鼠非酒精性脂肪肝发展中的作用

• 发表时间: 2007
• 作者: Matsumoto H;Fujii K;Nishitani Y;Okazaki S;Katada R;Umetani K.
• 通讯作者: Umetani K.