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作 者:刘庆丰[1] 刘毅[2] 焦正[1] 李中东[1] 施孝金[1] 钟明康[1]
机构地区:[1]复旦大学附属华山医院临床药学研究室,上海200040上海200040 [2]复旦大学附属华山医院中医科,上海200040
出 处:《中国药理学通报》2016年第6期868-873,共6页Chinese Pharmacological Bulletin
基 金:上海市卫计委资助项目(No 2010Y007A;20124053)
摘 要:目的研究三黄汤(SHD)对胰岛素抵抗3T3-L1脂肪细胞糖脂代谢的作用及可能的调控机制。方法高糖高胰岛素(含地塞米松)诱导3T3-L1脂肪细胞发生胰岛素抵抗,给予对照药物罗格列酮(Ros)或不同浓度SHD干预24 h,检测培养上清中葡萄糖减少(消耗)量、甘油和游离脂肪酸(NEFA)浓度以及细胞内甘油三酯(TG)含量;以2-脱氧-[3H]-葡萄糖摄入法观察脂肪细胞对葡萄糖的转运率;应用反转录-聚合酶链反应(RT-PCR)检测葡萄糖转运体4(GLUT-4)的mRNA表达水平,以Western blot检测GLUT-4蛋白的表达水平。结果与对照组相比,SHD的中高剂量(5、10、20、40 g·L^(-1))能使胰岛素抵抗脂肪细胞的葡萄糖消耗量和葡萄糖的转运率增加(P<0.01)、脂肪细胞内TG降低(P<0.01),细胞上清液中甘油的浓度不同程度增加(P<0.01),并明显减少NEFA的溢出,以上变化在三黄汤5~20g·L^(-1)范围内呈现量效关系;同时,Ros增加葡萄糖消耗、葡萄糖的转运率和细胞内TG积累(P<0.01),对培养上清中甘油、NEFA无明显影响(P>0.05)。SHD中、高剂量与Ros都能不同程度明显上调GLUT-4的mRNA和蛋白表达水平(P<0.01)。结论 SHD能明显增加3T3-L1脂肪细胞的葡萄糖摄取和消耗,促进细胞内TG分解,并减少NEFA溢出,通过调节糖代谢和脂代谢改善胰岛素抵抗。Aim To observe the effect of San Huang Decoction( SHD) on glucose and lipid metabolism ininsulin resistance( IR) 3T3-L1 adipocytes. Methods The IR model of 3T3-L1 adipocytes was induced by high glucose and hyperinsulinism cultivation( also containing dexamethasone). The adipocytes were treated with rosiglitazone( Ros) and different concentrations of SHD( 2. 5,5,10,20,40 g · L^(-1)) for 24 h. The content of glucose disappeared from the culture medium was determined as glucose consumption of the cells.The transport of glucose was observed by 2-deoxidation-[3H]-glucose uptake method. The efflux of nonesterified fatty acids( NEFA) from adipocytes was observed by the concentration of NEFA in the culture medium.The mRNA expression of glucose transporter-4( GLUT-4) was measured by real-time polymerase chain reaction( real-time PCR). The protein expression of GLUT-4 was detected by Western blot. Results Compared with the Con group,SHD( 5,10,20,40 g · L^(-1))could significantly induce the glucose consumption andtransportion( P < 0. 01),increase the glycerol content in culture supernatant( P < 0. 01),reduce the NEFA concentration in culture medium and accumulation of intracellular TG( P < 0. 01). And all of these change showed a concentration-dependent effect when SFD concentrations were from 5 g ·L^(-1) to 20 g · L^(-1). At the same time,Ros could also remarkably induce the glucose consumption and transportion( P < 0. 01),and increase the accumulation of intracellular TG( P <0. 01); but the concentration of NEFA and glycerol in culture medium did not show any difference in the Rostreated group( P > 0. 05). Conclusion SHD can increase insulin sensitivity by increasing glucose transportation and consumption in the 3T3-L1 adipocytes as well as decreasing the NEFA efflux from the cells.
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