摘要
探讨中药成分黄芩苷、小檗碱、葛根素和甘草苷对肝胰岛素抵抗(insulin resistance,IR)细胞糖代谢的改善作用。采用胰岛素和地塞米松联合诱导建立IR-HepG2细胞模型,给药24 h测定不同剂量黄芩苷、小檗碱、葛根素和甘草苷对葡萄糖消耗量、糖原含量和细胞活性的影响。结果显示,与IR模型组相比,除甘草苷和1μmol·L-1黄芩苷组外,各给药组均显著升高葡萄糖消耗量;黄芩苷组(10,20,50μmol·L-1)、小檗碱组(5,10,20,50μmol·L-1)和葛根素组(40,80,160μmol·L-1)显著增加细胞内肝糖原含量;而甘草苷降糖作用不明显。在此基础上,重点研究黄芩苷、小檗碱和葛根素对IR-HepG2细胞葡萄糖转运蛋白(GLUTs)表达水平的影响。q PCR结果显示IR-HepG2细胞GLUT1和GLUT4基因mRNA表达比正常组低。5,20μmol·L-1小檗碱下调IR-HepG2细胞GLUT1基因mRNA水平;20,40,80μmol·L-1葛根素上调GLUT1基因mRNA水平。10,20,50μmol·L-1黄芩苷和20μmol·L-1小檗碱上调GLUT4基因mRNA水平,40,80μmol·L-1葛根素下调GLUT4基因mRNA水平。Western blot法检测结果显示,与正常组相比,IR-HepG2细胞GLUT1和GLUT4蛋白表达降低,GLUT2表达升高。10,20,50μmol·L-1黄芩苷上调GLUT2和GLUT4蛋白表达;20μmol·L-1小檗碱升高GLUT2蛋白表达,10,20μmol·L-1小檗碱增加GLUT4蛋白表达;20,40,80μmol·L-1葛根素上调GLUT1和GLUT2蛋白表达。以上成分体外差异化影响GLUT1/2/4表达,可以有效调节葡萄糖转运的瞬时响应和长期响应。降糖途径分析显示黄芩苷和葛根素与油酸诱导IR-HepG2细胞降糖作用途径环节及效应强弱存在一定程度差异,而小檗碱和甘草苷在2种不同诱因的IR-HepG2细胞中无明显差异。体外研究初步表明黄芩苷、小檗碱和葛根素具有体外差异化降糖作用,可加速糖转运增加糖原合成调节糖代谢改善肝IR。
To investigate the hypoglycemic effects of baicalin,berberine,puerarin and liquiritin on the insulin resistance(IR)cells. The IR model of HepG2 cells was established by treatment with insulin and dexamethasone for 48 h. Glucose uptake,glycogen content and cell viability were detected with different concentrations of baicalin,berberine,puerarin,liquiritin in IR-HepG2 cells.Compared with IR model group,all of intervened groups significantly increased the glucose consumption,except for liquiritin groups and 1 μmol·L-1 baicalin group. Moreover,10,20,50 μmol·L-1 baicalin,5,10,20,50 μmol·L-1 berberine and 40,80,160μmol·L-1 puerarin significantly elevated glycogen content in IR-HepG2 cells. Liquiritin did not show obvious hypoglycemic effect.Compared with normal group,the mRNA expression levels of GLUT1 and GLUT4 were decreased in IR-HepG2 cells according to q PCR results. 5,20 μmol·L-1 berberine decreased the mRNA expression level of GLUT1 in IR-HepG2 cells,whereas 20,40,80 μmol·L-1 puerarin significantly elevated the mRNA expression level of GLUT1. Moreover,10,20,50 μmol·L-1 baicalin and 20 μmol·L-1 berberine increased the mRNA expression level of GLUT4. Whereas,40,80 μmol·L-1 puerarin decreased the mRNA expression level of GLUT4. Western blot results suggested that 10,20,50 μmol·L-1 baicalin significantly increased the protein expressions of GLUT2 and GLUT4,whereas 20,40,80 μmol·L-1 puerarin significantly up-regulated GLUT1 and GLUT2 proteins. In addition,20 μmol·L-1 berberine increased the protein expressions of GLUT2 and GLUT4,whereas 10 μmol·L-1 berberine up-regulated GLUT4 expression. The results preliminarily suggested that baicalin,berberine and puerarin have differentiated hypoglycemic effects,which accelerate glucose transport,increase glycogen synthesis,regulate glucose metabolism and improve hepatic IR.
作者
涂珺
朱水兰
周小妹
TU Jun;ZHU Shui-lan;ZHOU Xiao-mei(Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis,Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory,Jiangxi University of Traditional Chinese Medicine Nangchang330004;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanehang 330004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2018年第20期4097-4103,共7页
China Journal of Chinese Materia Medica
基金
江西省自然科学基金项目(20143ACB20010,20171BAB205094)
江西省卫生厅中医药科技计划项目(2017Z017)
国家自然科学基金项目(81460621)
