CHOLINE OR CDP-CHOLINE ALTERS SERUM LIPID RESPONSES TO ENDOTOXIN IN DOGS AND RATS: INVOLVEMENT OF THE PERIPHERAL NICOTINIC ACETYLCHOLINE RECEPTORS
CHOLINE OR CDP-CHOLINE ALTERS SERUM LIPID RESPONSES TO ENDOTOXIN IN DOGS AND RATS: INVOLVEMENT OF THE PERIPHERAL NICOTINIC ACETYLCHOLINE RECEPTORS
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DOI：
10.1097/shk.0b013e3181971b02
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发表时间：
2009-09-01
期刊：
影响因子：
3.1
通讯作者：
Ulus, Ismail H.
中科院分区：
文献类型：
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作者：
Ilcol, Yesim Ozarda;Yilmaz, Zeki;Ulus, Ismail H.
我们之前表明，给予胆碱可以保护狗免受内毒素引起的多器官损伤和血小板功能障碍。由于败血症/内毒素血症与脂质代谢的改变有关，因此我们研究了胆碱或胆碱供体胞苷-5'-二磷酸胆碱是否会改变狗和大鼠对内毒素的血清脂质反应。在内毒素的作用下，甘油三酯、含胆碱磷脂、总胆固醇和高密度脂蛋白胆固醇的血清浓度以剂量和时间相关的方式增加。内毒素治疗前 5 分钟以及治疗后 4 和 8 小时给予胆碱（狗 20 mg/kg 静脉注射，大鼠 90 mg/kg 腹腔注射）或胞苷-5'-二磷酸胆碱（狗 70 mg/kg 静脉注射）可阻断或减弱血清甘油三酯、总胆固醇和非酯化脂肪酸的增加。内毒素引起的血清磷脂水平升高在大鼠中没有变化，而在狗中则因胆碱而增强。在大鼠中，对内毒素的血清脂质反应伴随着肝肾损伤标志物血清水平的数倍升高。它们的升高也被胆碱阻断。六甲铵预处理可阻断胆碱对血脂和肝肾损伤标志物的影响。阿托品预处理可阻止内毒素引起的血脂和肝肾损伤标志物升高，但未能改变胆碱对这些参数的作用。胆碱治疗提高了致死性内毒素休克大鼠的存活率。总之，这些数据表明胆碱治疗改变了血清脂质对内毒素的反应，并通过烟碱乙酰胆碱受体介导的机制预防内毒素血症期间的肝肾损伤。因此，胆碱和含胆碱化合物可能具有治疗内毒素血症/败血症的治疗潜力。
We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.