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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细胞功能紊乱状态,可能与其降低MSG小鼠胰腺中炎症反应有关。
Objective To investigate the effects of Mudan Granule (MD) on glucose metabolism and pancreatic β-cell function in mice with insulin resistance induced by monosodium glutamate (MSG). Methods MSG mice were injected subcutaneously with MSG on the 7th day to select 40 MSG mice with insulin resistance characteristics. According to body weight, fasting blood glucose, lipids TG, TC and percentage of decline in 40min blood glucose in insulin tolerance test, Divided into 4 groups, including model group (Con group), MD group low, high dose group and metformin group (Met group), another 10 ICR mice were normal control group (Nor group), MD low dose group and high Dose group were given 2.5,5 g / kg body weight of dry powder material aqueous solution of solvent, Met group given 0.2g / kg weight of metformin hydrochloride solution, Nor and Con groups were given equal doses of distilled water, Medicine 1 time, administration time 15 weeks. (ITT) and oral glucose tolerance test (OGTT) during the course of treatment. The function of β-cell was evaluated by hyperglycemic clamp technique. The changes of nitric oxide stress-related index (ONOO-, iNOS) in pancreas of MSG mice were determined. The changes of pancreatic islet pathological changes were observed. The levels of iNOS, NF-κB p65 and phosphorylated protein (p-NF-κB p65) in pancreatic tissue were detected. Results Compared with Nor group, the levels of blood glucose, AUC, fasting serum insulin, ONOO-, iNOS activity, iNOS expression, NF-κB p65 subunit expression and p-NF-κB p65 expression in Con group at each time point (P <0.05, P <0.01). The expression of subunit mRNA and protein were significantly increased in ITT group at 40 min after treatment with ITT, the GIR, the first phase and the maximal insulin secretion decreased significantly (P <0.05, P <0.01). Compared with the Con group, the Met group could improve the above indexes (P <0.05, P <0.01); AUC, iNOS activity, iNOS expression and p-NF-κB p65 subunit expression in OGTT and ITT (P <0.05, P <0.01). The AUC, ONOO-content, iNOS activity, iNOS expression, NF-κB p65 subunit of OGTT and ITT in the high MD group (P <0.05, P <0.01). The expression of p65 and NF-κB p65 subunit were significantly decreased in ITT group. The percent of blood glucose, GIR and maximal insulin secretion in ITT 40min group were significantly increased (P <0.05, P <0.01). Conclusion Mudan granules can significantly improve insulin resistance and β-cell dysfunction status in obese insulin resistance MSG mice, which may be related to the reduction of inflammation in the pancreas of MSG mice.