选择性alpha7-nicotinic乙酰胆碱受体激动剂GTS-21改善生存在小鼠内毒素和严重脓毒症。

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巴甫洛夫VA,杨Ochani M, LH, Gallowitsch-Puerta M, Ochani K,林X,李维J,帕里什WR, Rosas-Ballina M, Czura CJ, Larosa GJ,米勒EJ,特蕾西KJ, Al-Abed Y

选择性alpha7-nicotinic乙酰胆碱受体激动剂GTS-21改善生存在小鼠内毒素和严重脓毒症。

暴击治疗地中海。2007年4月,35 (4):1139 - 44。

PubMed ID

17334244 (在PubMed

]

文摘

目的:肿瘤坏死因子和高机动组盒1是至关重要的细胞因子炎症介质。通过alpha7-nicotinic传出迷走神经抑制细胞因子释放乙酰胆碱受体介导胆碱能信号。这里我们研究是否GTS-21,选择性alpha7-nicotinic乙酰胆碱受体激动剂,抑制促炎细胞因子在体外和体内,提高生存在小鼠内毒素和严重脓毒症。设计:随机和控制在体外和体内研究。设置:研究实验室和动物设必威国际app施的房间。主题:264.7原始细胞和BALB / c小鼠内毒素或受到盲肠的结扎和穿刺(CLP)。干预措施:264.7原始细胞暴露于内毒素(4 ng / mL或10 ng / mL)的存在与否GTS-21(1 - 100妈妈)和肿瘤坏死因子和高机动组盒1释放和核factor-kappaB活化进行了分析。老鼠GTS-21处理(0.4毫克/公斤或4毫克/公斤,腹腔内)或盐碱前30分钟内毒素(6毫克/公斤,腹腔内)和血清肿瘤坏死因子分析了1.5小时后内毒素。在生存实验中,小鼠接受GTS-21(0.4或4.0毫克/公斤,腹腔内)或生理盐水30分钟之前和内毒素后6小时,然后连续3天每天两次。严重脓毒症是由中电。 Mice were treated with GTS-21 (4 mg/kg) or saline immediately and 6 hrs and 24 hrs after CLP, and serum high mobility group box 1 was analyzed 30 hrs after CLP. In survival experiments, GTS-21 (0.4 or 4 mg/kg) treatment was initiated 24 hrs after CLP and continued twice daily for 3 days. MEASUREMENTS AND MAIN RESULTS: GTS-21 dose-dependently inhibited tumor necrosis factor and high mobility group box 1 release and nuclear factor-kappaB activation in vitro. GTS-21 (4 mg/kg) significantly inhibited serum tumor necrosis factor during endotoxemia and improved survival (p < .0001). GTS-21 (4 mg/kg) significantly inhibited serum high mobility group box 1 levels in CLP mice and improved survival (p < .0006). CONCLUSION: These findings are of interest for the development of alpha7-nicotinic acetylcholine receptor agonists as a new class of anti-inflammatory therapeutics.

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药物靶点

药物	目标	类	生物	药理作用	行动
GTS-21	神经乙酰胆碱受体亚单位级别alpha - 7	蛋白质	人类	未知的	不可用	细节