益气养阴清热方对KKAy小鼠GLP-2、IFN-γ、NF-κB的影响
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摘要
目的探讨益气养阴清热方对自发性2型糖尿病(KKAy)小鼠胰高血糖素样肽2(glucagon-like peptide 2, GLP-2)、γ干扰素(interferon gamma, IFN-γ)、核因子κB(nuclear factor kappa beta, NF-κB)的影响。方法取雄性SPF级KKAy小鼠50只,随机分为模型组,二甲双胍组,益气养阴清热方高、中、低剂量组,每组各10只;另取10只C57BL/6J小鼠作为正常组。各组予以相应干预。干预8周后检测各组小鼠GLP-2、IFN-γ、NF-κB水平。结果与正常组比较,模型组小鼠IFN-γ、NF-κB明显升高(P<0.01),GLP-2水平明显降低(P<0.01)。益气养阴清热方高、中、低剂量组均可降低KKAy小鼠IFN-γ水平(P<0.05);益气养阴清热方高剂量组可降低小鼠NF-κB水平(P<0.05);益气养阴清热方高、中、低剂量组均可升高小鼠GLP-2水平(P<0.05)。结论益气养阴清热方能改善糖尿病小鼠血糖、胰岛素抵抗,其作用可能与提高GLP-2水平、降低炎症反应相关。
Objective To investigate the effects of Yiqi Yangyin Qingre Formula on glucagon-like peptide 2(GLP-2),interferon-gamma(IFN-γ) and nuclear factor kappa B(NF-κB) in spontaneous type 2 diabetes(KKAy) mice. Methods A total of50 male SPF KKAy mice were selected. They were randomly divided into a model group, a metformin group, as well as high, medium and low dose groups of Yiqi Yangyin Qingre Formula, with 10 mice in each group. And 10 C57 BL/6 J mice were taken as the normal group. Each group was given corresponding intervention. After 8 weeks of intervention, the levels of GLP-2,IFN-γ and NF-κB of mice were measured. Result Compared with the normal group, the levels of IFN-γ and NF-κB in the model group were increased significantly(P<0.01), and the GLP-2 level was decreased significantly(P<0.01). The IFN-γ level of KKAy mice could be decreased in the high, medium and low dose groups of Yiqi Yangyin Qingre Formula(P<0.05). The NF-κB level of mice could be decreased in the high dose group of Yiqi Yangyin Qingre Formula(P<0.05). And the GLP-2 level of mice could be increased in the high, medium and low dose groups of Yiqi Yangyin Qingre Formula(P<0.05). Conclusion Yiqi Yangyin Qingre Formula can reduce blood glucose and insulin resistance in diabetic mice, and its effects may be related to the increase of GLP-2 level and the reduction of inflammatory reaction.
Objective To investigate the effects of Yiqi Yangyin Qingre Formula on glucagon-like peptide 2(GLP-2),interferon-gamma(IFN-γ) and nuclear factor kappa B(NF-κB) in spontaneous type 2 diabetes(KKAy) mice. Methods A total of50 male SPF KKAy mice were selected. They were randomly divided into a model group, a metformin group, as well as high, medium and low dose groups of Yiqi Yangyin Qingre Formula, with 10 mice in each group. And 10 C57 BL/6 J mice were taken as the normal group. Each group was given corresponding intervention. After 8 weeks of intervention, the levels of GLP-2,IFN-γ and NF-κB of mice were measured. Result Compared with the normal group, the levels of IFN-γ and NF-κB in the model group were increased significantly(P<0.01), and the GLP-2 level was decreased significantly(P<0.01). The IFN-γ level of KKAy mice could be decreased in the high, medium and low dose groups of Yiqi Yangyin Qingre Formula(P<0.05). The NF-κB level of mice could be decreased in the high dose group of Yiqi Yangyin Qingre Formula(P<0.05). And the GLP-2 level of mice could be increased in the high, medium and low dose groups of Yiqi Yangyin Qingre Formula(P<0.05). Conclusion Yiqi Yangyin Qingre Formula can reduce blood glucose and insulin resistance in diabetic mice, and its effects may be related to the increase of GLP-2 level and the reduction of inflammatory reaction.
引文
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[12] KIECHL S, WITTMANN J, GIACCARI A, et al. Blockade of receptor activator of nuclear factor-κB(RANKL)signaling improves hepatic insulin resistance and prevents development of diabetes mellitus[J]. Nature Medicine, 2013,19(3):358-363.
[13] SHI H, KOKOEVA M V, INOUYE K, et al. TLR4 links innate immunity and fatty acid-induced insulin resistance[J].The Journal of Clinical Investigation, 2006,116(11):3015-3025.
[14] CAMERON H L, PERDUE M H. Stress impairs murine intestinal barrier function:improvement by glucagon-like peptide-2[J]. The Journal of Pharmacology and Experimental Therapeutics, 2005,314(1):214-220.
[15]仝小林.糖尿病中医药临床循证实践指南[M].北京:科学出版社,2016:19.
[16]张翔,喻嵘,曾婧,等.从“热”论消渴[J].湖南中医药大学学报,2015,35(6):27-31.
[2] GUAN X, STOLL B, LU X, et al. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1[J]. Gastroenterology, 2003,125(1):136-147.
[3] GELONEZE B, LIMA M M, PAREJA J C, et al. Association of insulin resistance and GLP-2secretion in obesity:a pilot study[J].Arquivos Brasileiros de Endocrinologia&Metabologia, 2013,57(8):632-635.
[4] SHI X, ZHOU F G, CHANG B, et al. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons[J]. Cell Metabolism, 2013,18(1):86-98.
[5] SHAN C Y, YANG J H, KONG Y, et al. Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated Type2 diabetic rats[J]. Journal of Endocrinology, 2013, 218(3):255-262.
[6]李双蕾,陈文辉,陈莉娜,等.益气养阴清热方对初发2型糖尿病患者胰岛素抵抗的影响[J].广西中医药,2012,35(4):9-12.
[7]李双蕾,陈莉娜,赵伟,等.益气养阴清热方对2型糖尿病患者炎症因子的影响[J].中华中医药杂志,2013,28(3):474-748.
[8]蒋云霞,李双蕾,陈文辉,等.益气养阴清热方对糖尿病KKAy小鼠血清胰岛素及TNF-α、IL-6的影响[J].世界中西医结合杂志,2018,13(9):1248-1251.
[9]刘晓丹,杨刚,范秋灵,等.自发性2型糖尿病动物模型KKAy小鼠肾脏损害的特征与演变[J].中国医科大学学报,2011,40(2):104-106.
[10] SCHMIDT F M, WESCHENFELDER J, SANDER C, et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity[J]. PloS ONE, 2015,10(3):e0121971.
[11] GUZIK T J, SKIBA D S, TOUYZ R M, et al. The role of infiltrating immune cells in dysfunctional adipose tissue[J]. Cardiovascular Research, 2017,113(9):1009-1023.
[12] KIECHL S, WITTMANN J, GIACCARI A, et al. Blockade of receptor activator of nuclear factor-κB(RANKL)signaling improves hepatic insulin resistance and prevents development of diabetes mellitus[J]. Nature Medicine, 2013,19(3):358-363.
[13] SHI H, KOKOEVA M V, INOUYE K, et al. TLR4 links innate immunity and fatty acid-induced insulin resistance[J].The Journal of Clinical Investigation, 2006,116(11):3015-3025.
[14] CAMERON H L, PERDUE M H. Stress impairs murine intestinal barrier function:improvement by glucagon-like peptide-2[J]. The Journal of Pharmacology and Experimental Therapeutics, 2005,314(1):214-220.
[15]仝小林.糖尿病中医药临床循证实践指南[M].北京:科学出版社,2016:19.
[16]张翔,喻嵘,曾婧,等.从“热”论消渴[J].湖南中医药大学学报,2015,35(6):27-31.