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番石榴叶三萜化合物乌苏酸对3T3-L1前脂肪细胞增殖、分化及胰岛素抵抗的影响

Effects of Triterpenoid from Psidium guajava Leaves Ursolic Acid on Proliferation,Differentiation of 3T3-L1 Preadipocyte and Insulin Resistance

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【作者】 林娟娜匡乔婷叶开和叶春玲黄仪张晓琦叶文才

【Author】 LIN Juan-na;KUANG Qiao-ting;YE Kai-he;YE Chun-ling;HUANG Yi;ZHANG Xiao-qi;YE Wen-cai;Jinan University;Department of Pharmacy,Hubei Xiangfan First people’ s Hospital;

【机构】 暨南大学湖北省襄樊市第一人民医院药剂科

【摘要】 目的:探讨番石榴叶三萜化合物乌苏酸对3T3-L1前脂肪细胞增殖、分化及胰岛素抵抗的影响及其机制。方法:培养3T3-L1前脂肪细胞,给予不同药物作用48 h后,采用MTT法检测对细胞增殖的影响;采用油红-O染色法对细胞分化的影响。以地塞米松诱导分化成熟的脂肪细胞,建立胰岛素抵抗模型,给予相应的药物后干预48 h。采用GOD-POD法、比色法和ELISA法检测细胞培养上清液中葡萄糖、游离脂肪酸含量及脂联素水平;Western blotting分析脂肪细胞中PPARγ和PTP1B的表达。结果:与溶媒对照组比较,30、100μmol/L乌苏酸能显著促进3T3-L1前脂肪细胞增殖及分化(P<0.05或P<0.01)。乌苏酸在30μmol/L时即可显著增加胰岛素抵抗脂肪细胞葡萄糖消耗,同时能明显减少胰岛素抵抗脂肪细胞游离脂肪酸的产生(P<0.05),也能显著促进脂联素分泌(P<0.05);在100μmol/L时上调PPARγ蛋白表达(P<0.05),但对PTP1B蛋白表达无明显影响(P>0.05)。结论:乌苏酸促进3T3-L1前脂肪细胞增殖和分化,增加脂肪细胞葡萄糖摄取,抑制游离脂肪酸产生,促进脂联素分泌,对脂肪细胞胰岛素抵抗有明显的改善作用,其机制可能与上调PPARγ蛋白表达、提高胰岛素敏感性有关。

【Abstract】 Objective: To investigate the influences of triterpenoid from Psidium guajava Leaves( ursolic acid) on the proliferation,differentiation of 3T3-L1 preadipocyte,and its possible mechanism treat for insulin resistance. Methods: 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h,the cell viability was tested by MTT assay. Induced for 6 days,the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARγ and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Results: Compared with medium control group,30、100 μmol / L ursolic acid could increase its proliferation and differentiation significantly( P < 0. 05 or P < 0. 01). Compared with the model group,ursolic acid at 100 μmol / L could enhance cellular glucose uptake of insulin resistant adipocyte significantly both in basic and insulin stimulation state( P < 0. 01),while ursolic acid at 30 μmol / L could already enhance its glucose uptake significantly( P < 0. 05),and could already decrease its FFA production significantly( P < 0. 05).Ursolic acid at 30 μmol / L could increase the secretion of adiponectin on insulin resistant adipocyte significantly( P < 0. 05),up-regulate the expression of PPARγ protein( P < 0. 05),but showed no effect on the PTP1B protein expression( P > 0. 05). Conlusion: Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte,enhance cellular glucose uptake,inhibit the production of FFA,promote the secretion of adiponectin insulin resistant adipocyte,its mechanism may be related to upregulating the expression of PPARγ protein.

【基金】 广东省高等学校科技创新重点项目(cxzd1111);国家“重大新药创新”科技重大项目(2012zx09103201-056);国家自然科学基金(81373935);中央高校基本科技业务费专项资金项目(21612203)
  • 【文献出处】 中药材 ,Journal of Chinese Medicinal Materials , 编辑部邮箱 ,2013年08期
  • 【分类号】R285.5
  • 【被引频次】12
  • 【下载频次】391
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