摘要
目的研究木丹颗粒(Mudan Granule,MD)对谷氨酸钠(monosodium glutamate,MSG)诱导的肥胖性胰岛素抵抗小鼠糖代谢及胰岛β细胞功能的影响。方法新生小鼠连续7日皮下注射MSG形成模型动物,选40只具有胰岛素抵抗特征的MSG小鼠,依照体重、空腹血糖、血脂TG、TC以及胰岛素耐量试验中40min血糖下降百分数5个指标,随机分为4组,包括模型组(Con组),MD组低、高剂量组和二甲双胍组(Met组),另取10只ICR小鼠为正常对照组(Nor组),MD低剂量组和高剂量组分别给予2.5、5g/kg体重的原料药干膏粉水溶剂,Met组给予0.2g/kg体重的盐酸二甲双胍水溶液,Nor组和Con组均给予等剂量配药溶剂蒸馏水,每日灌胃给药1次,给药时长15周。期间进行胰岛素耐量(ITT)和口服葡萄糖耐量试验(OGTT);采用高血糖钳夹技术评价β细胞功能;测定MSG小鼠胰腺中硝化应激相关指标(ONOO-、iNOS)的改变;胰腺组织HE染色,观察胰岛病理形态的变化;检测胰腺中炎症相关因子蛋白iNOS和NF-κB p65及其磷酸化蛋白(p-NF-κB p65)水平的改变。结果与Nor组比较,Con组的OGTT及ITT实验各时间点的血糖水平、AUC以及空腹血清胰岛素、ONOO-含量、iNOS活性、iNOS表达、NF-κB p65亚基表达、p-NF-κB p65亚基表达均明显升高,ITT实验40min血糖下降百分数、葡萄糖输注速率(GIR)、一相及最大胰岛素分泌均明显降低(P<0.05,P<0.01)。与Con组比较,Met组可改善上述各项指标(P<0.05,P<0.01);MD低组OGTT及ITT实验的AUC、iNOS活性、iNOS表达、p-NF-κB p65亚基表达均明显下降,ITT实验40min血糖下降百分数及GIR均明显升高(P<0.05,P<0.01);MD高组OGTT及ITT实验的AUC、ONOO-含量、iNOS活性、iNOS表达、NF-κB p65亚基表达、p-NF-κB p65亚基表达均明显下降,ITT实验40min血糖下降百分数、GIR以及最大胰岛素分泌均明显升高(P<0.05,P<0.01)。结论木丹颗粒可显著改善肥胖性胰岛素抵抗MSG小鼠的胰岛素抵抗和β细胞功能紊乱�
Objective To study the effect of Mudan Granule （MD） on the glucose metabolism and beta cell function in monosodium glutamate （MSG） induced obese mice with insulin resistance （IR）. Methods MSG obese mice were induced by subcutaneous injecting MSG （4 g/kg for 7 successive days in neonatal ICR mice）. Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride （TG）, total cholesterol （TC）, and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group （Con）, the low dose MD group, the high dose MD group, and the Metformin group （Met）. Besides, another 10 ICR mice were recruited as the normal control group （Nor）. The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test （ITT） and oral glucose tolerance test （OGTT） were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin （HE） staining. Changes of iNOS, NF-κB p65, and p-NF-κB p65 in the pancreas were tested. Results Compared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-κB p65 subunit, p- NF-κB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate （GIR）, Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group （P〈0.05, P〈0.01）. Compared with the Con group, the aforesaid indices could be improved in the Met group （P 〈0.05, P 〈0.01）. In the low dose
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2014年第7期853-858,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
重大新药创制国家科技重大专项-心脑血管病
糖尿病并发症
神经退行性疾病药物药效学评价(No.2012ZX09301002-004)
