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重组瘦素可促进载脂蛋白E缺乏小鼠的动脉粥样硬化和血栓形成。

Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice.

作者信息

Bodary Peter F, Gu Shufang, Shen Yuechun, Hasty Alyssa H, Buckler Joshua M, Eitzman Daniel T

机构信息

Division of Cardiovascular Medicine, Department of Internal Medicine, niversity of Michigan Medical Center, Ann Arbor, MI, USA.

出版信息

Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):e119-22. doi: 10.1161/01.ATV.0000173306.47722.ec. Epub 2005 Jun 9.

Abstract

OBJECTIVE

The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic-prone mice.

METHODS AND RESULTS

Sixteen-week-old, male apolipoprotein E-deficient mice were treated with injections of recombinant leptin (125 microg per day IP; n=10) or vehicle (n=10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352+/-30.7 versus 621+/-61.5 mg; P=0.005) and fasting insulin (0.57+/-0.25 versus 1.7+/-0.22 ng/mL; P=0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis (8.0+/-0.95% versus 5.4+/-0.59% lesion surface coverage; P<0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury (21+/-2.1 versus 34.6+/-5.4 minutes; P=0.045).

CONCLUSIONS

These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.

摘要

目的

瘦素在血管疾病中的直接作用仍存在争议。本研究的目的是检测瘦素治疗对易患动脉粥样硬化小鼠的动脉粥样硬化和血栓形成的影响。

方法与结果

对16周龄雄性载脂蛋白E缺陷小鼠进行治疗,一组每天腹腔注射重组瘦素(125微克;n = 10),另一组注射溶媒(n = 10),持续4周。瘦素治疗使附睾脂肪减少(352±30.7对621±61.5毫克;P = 0.005),空腹胰岛素水平降低(0.57±0.25对1.7±0.22纳克/毫升;P = 0.014)。尽管有这些代谢益处,但瘦素治疗却导致动脉粥样硬化增加(病变表面覆盖率8.0±0.95%对5.4±0.59%;P < 0.05)。瘦素治疗还使血管损伤后发生闭塞性血栓形成的时间缩短(21±2.1对34.6±5.4分钟;P = 0.045)。

结论

这些研究表明,外源性瘦素会促进动脉粥样硬化和血栓形成,并支持瘦素水平升高可能增加心血管疾病风险这一观点。

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