黄连改善胰岛素抵抗药效物质基础研究

Pharmacodyamic material basis of Rhizoma Coptidis on insulin resistance

目的:从细胞途径多方面观察黄连药材、部位及其成分等对3T3-L1前脂肪细胞诱导分化及脂肪细胞胰岛素抵抗的影响,探索黄连改善胰岛素抵抗的药效物质基础。方法:培养3T3-L1前脂肪细胞,采用地塞米松、3-异丁基-1-甲基黄嘌呤和胰岛素共同诱导3T3-L1前脂肪细胞分化为脂肪细胞,并建立胰岛素抵抗模型。依据黄连传统用药经验,观察黄连"药材-部位-生物碱成分"对脂肪细胞分化的影响,对胰岛素抵抗模型细胞培养液中葡萄糖消耗的影响。结果:除非生物碱部位在6.0μg.L-1具有明显促进分化作用外,其余各组无论黄连水提物、不同提取部位还是不同生物碱成分均能明显抑制3T3-L1前脂肪细胞的分化,其中单体成分盐酸黄连碱在浓度16.5μmol.L-1时抑制作用最为明显;同时,各组也均能降低培养液中葡萄糖的含量,提高葡萄糖的利用率,改善胰岛素抵抗,作用与马来酸罗格列酮相似,其中单体成分盐酸药根碱在浓度10.5μmol.L-1时改善作用明显优于其余各成分。结论:黄连具有明显改善胰岛素抵抗,抑制前脂肪细胞分化的作用,其疗效可能是各成分协同作用的结果;同时其抑制分化作用也提示黄连在增加细胞对葡萄糖摄取的同时不会引起脂肪的聚集而造成体重增加,这对防治与胰岛素抵抗相关的代谢综合征或并发症具有一定临床意义。

Objective： To observe the impact of Rhizoma Coptidis（drug-chemical extract parts-components） on 3T3-L1 pre-adipocytes differentiation and adipocytes insulin resistance,and reveal the pharmacodyamic material basis of Rhizoma Coptidis on insulin resistance.Method： 3T3-L1 pre-adipocytes were well cultured,and then induced to differentiate into fat cells by using dexamethasone,3-isobutyl-1-methyl-xanthine and insulin together,and establish the insulin resistance model.Based on the experience of traditional medicine use,the adipocytes differentiation and the glucose consumption in the cell culture medium were observed independently.Result： Aqueous extract,different chemical extract fraction and different alkaloid extract from the herb showed inhibitory effects on 3T3-L1 pre-adipocytes differentiation,especially the compound coptisine significantly inhibited the differentiation in the concentration of 16.5 μmol·L-1,but non-alkaloid extract from the herb promoted cell differentiation significantly in the concentration of 6.0 μmol·L-1.Each treatment group,especially jatrorrhizine hydrochloride（in the concentration of 10.5 μmol·L-1） significantly decreased the concentration of glucose in 3T3-L1 adipocytes culture,at the same time improved insulin resistance.These effects are similar to the role of rosiglitazone maleate.Conclusion： Rhizoma Coptidis significantly improved insulin resistance,prevented pre-adipocytes differentiation.Its efficacy may be the synergistic effect of various components.Meanwhile,its role in inhibiting differentiation of pre-adipocytes indicates that coptis to increasing glucose uptake dose not cause fat accumulation and weight increasing.This has some clinical significance in the insulin resistance and metabolic syndrome.