辛伐他汀对胰岛素抵抗大鼠脂肪组织脂联素和核因子κB抑制因子激酶mRNA表达的影响
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辽宁省自然科学基金(20042094);辽宁省教育厅高等学校科学技术研究项目(2004D192)


Effect of Simvastatin on Adiponectin and Nuclear Factor-Kappa B Inhibitor Kinase mRNA Expression in Adipose Tissue of Insulin Resistant Rats
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    摘要:

    目的探讨辛伐他汀对胰岛素抵抗大鼠脂肪组织脂联素和核因子κB抑制因子激酶mRNA表达的影响。方法采用高脂饲料喂养复制胰岛素抵抗大鼠模型,并用正常血糖—高血浆胰岛素钳夹技术评估。胰岛素抵抗大鼠给予辛伐他汀10mg/(kg.d)治疗。应用逆转录聚合酶链反应检测大鼠脂肪组织中脂联素和核因子κB抑制因子激酶mRNA的表达。结果高脂饲料喂养组大鼠葡萄糖输注率明显低于基础饲料喂养组[0.76±0.28mg/(kg.min)比4.26±0.70mg/(kg.min),P<0.01]。辛伐他汀治疗组和高脂未治疗组大鼠脂肪组织中脂联素mRNA的表达差异无显著性(0.25±0.12比0.29±0.11,P>0.05),但均明显低于基础饲料喂养组(1.18±0.12,P<0.05)。辛伐他汀治疗组大鼠脂肪组织中核因子κB抑制因子激酶mRNA的表达明显低于高脂未治疗组(0.15±0.03比1.21±0.03,P<0.05),与基础饲料喂养组差异无显著性(0.15±0.03,P>0.05)。除外辛伐他汀干预作用后大鼠脂肪组织脂联素与核因子κB抑制因子激酶mRNA的表达负相关(r=-0.97,P=0.000)。结论辛伐他汀不能增加高脂诱导的胰岛素抵抗大鼠脂肪组织脂联素mRNA的表达,但能使升高的核因子κB抑制因子激酶mRNA表达水平得以恢复,这可能得益于辛伐他汀调脂作用外的抗炎作用。

    Abstract:

    Aim To study the effect of simvastatin on adiponectin(APN)and nuclear factor-kappa B inhibitor kinase(IKK)mRNA expression in adipose tissue of insulin resistant rats.Methods Insulin resistant rat model was induced by high-fat diet feeding.Twenty-five male Wistar rats were randomly divided into two groups fed with either basic chow(n=10)or high-fat diet(n=15)for 10 weeks,then assessed by euglycemic-hyperinsulinemia clamp technique.And rats in high-fat group were randomly divided into simvastatin intervention group(n=5)and non-simvastatin intervention group(n=5).Rats in simvastatin intervention group were fed with simvastatin 10 mg/(kg·d)in gavage.After 5 weeks intervenient treatment,APN and IKK mRNA expressions were tested with RT-PCR.Results The glucose infusion rate(GIR)in high-fat group decreased significantly compared with basic chow group 0.76±0.28 mg/(kg·min)vs 4.26±0.70 mg/(kg·min),P<0.01.There were no obvious difference on APN mRNA expression of adipose tissue between simvastatin intervention group and non-simvastatin intervention group(0.25±0.12 vs 0.29±0.11,P>0.05);but they decreased significantly compared with basic chow group respectively(1.18±0.12,P<0.05).IKK mRNA expression of adipose tissue in simvastatin intervention group decreased significantly compared with non-simvastatin intervention group(0.15±0.03 vs 1.21±0.03,P<0.05),with no obvious difference from basic chow group(0.15±0.03,P>0.05).Conclusion Simvastatin could not increase APN mRNA expression in adipose tissue of insulin resistant rats induced by high-fat diet feeding.But simvastatin may restore IKK mRNA expression in adipose tissue of insulin resistant rats induced by high-fat diet feeding,which maybe benefit from the anti-inflammatory effect beyond the lipid-lowering effect.

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都健,崔丽娟,王娟,王慧敏.辛伐他汀对胰岛素抵抗大鼠脂肪组织脂联素和核因子κB抑制因子激酶mRNA表达的影响[J].中国动脉硬化杂志,2008,16(7):527~531.

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  • 收稿日期:2008-04-08
  • 最后修改日期:2008-06-28
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