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秋水仙碱联合阿托伐他汀对高脂血症大鼠的协同作用。

Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia.

机构信息

The Department of Internal Medicine, the Second Affiliated Hospital of Shantou University, Shantou, China.

出版信息

Lipids Health Dis. 2014 Apr 17;13:67. doi: 10.1186/1476-511X-13-67.

DOI:10.1186/1476-511X-13-67
PMID:24742015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4005013/
Abstract

BACKGROUND

Inflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown.

METHODS

Hyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed.

RESULTS

Before the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin.

CONCLUSION

Colchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.

摘要

背景

在高脂血症的情况下,炎症和内皮功能障碍与动脉粥样硬化的发生和发展有关。秋水仙碱是一种有效的抗炎药物,秋水仙碱联合阿托伐他汀是否对改善炎症和内皮功能具有协同作用尚不清楚。

方法

通过高脂高胆固醇饮食喂养 6 周制备高脂血症大鼠模型。正常饮食的大鼠作为对照组。在高脂血症组,给予生理盐水、阿托伐他汀(10mg/kg 体重/天)、秋水仙碱(0.5mg/kg 体重/天)或阿托伐他汀联合秋水仙碱(相同剂量)治疗 2 周。连续检测血脂谱、C 反应蛋白(CRP)、肝酶、脂蛋白相关磷脂酶 A2(Lp-PLA2)和一氧化氮(NO)的产生水平。

结果

在研究开始前,各组间所有实验室变量均无差异。在高脂血症模型制作 6 周后,与对照组相比,血清胆固醇、CRP 和 Lp-PLA2 水平显著升高,而 NO 水平降低。秋水仙碱治疗 2 周后,秋水仙碱组 CRP 和 Lp-PLA2 水平降低,NO 水平升高,且这种作用与降脂作用无关。阿托伐他汀联合秋水仙碱治疗进一步提高了 NO 水平,降低了 CRP 和 Lp-PLA2 水平,表明秋水仙碱和阿托伐他汀具有潜在的协同作用。

结论

秋水仙碱联合阿托伐他汀可能对改善高脂血症大鼠的内皮功能和炎症具有更强的保护作用。

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