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。澄清说，乙醇通过NF-kappab激活和Akt.2的激活来调节细胞存活系统。在非酒精性脂肪肝病鼠模型中，急性乙醇治疗没有通过NF-kappab引起促炎反应，这表明炎症性疾病发生在脂肪肝病中3。多不饱和脂肪酸会导致脂肪肝的严重炎症。然后多不饱和脂肪酸在肝细胞中诱导的IL-10释放，这可能会诱导库普弗细胞的激活4。我们建立了与酒精有关的猝死模型。在此模型中，TLR4信号通路在死亡原因中没有重要作用。5。在大脑挫伤模型中，先前的乙醇注射会促进创伤性脑损伤后的脑水肿。促进脑水肿会导致死亡。乙醇注射后的脑挫伤不会引起促炎细胞因子的任何释放和NF-kappab的激活，NF-kappab是细胞存活信号转录因子。 TBI后的N-乙酰基胱氨酸治疗减少了脑水肿以保持生存率6。我们建立了一个具有类固醇诱导的股骨骨坏死的模型。在此模型中，TLR4信号传导在股骨头的骨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

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.

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.

Regulation of activated Akt in JNK activation under ethanol loading

乙醇负载下 JNK 活化中活化 Akt 的调节

• 发表时间: 2004
• 作者: Nishitani Y;Fujii 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.