[1]刘海逸,张欣荣,岳晓丹,等.黄连解毒汤对糖耐量减低大鼠的糖尿病 延缓作用[J].国际内分泌代谢杂志,2017,37(03):149-154.[doi:10.3760/cma.j.issn.1673-4157.2017.03.002]
　Liu Haiyi*,Zhang Xinrong,Yue Xiaodan,et al.Effects of huang-lian-jie-du-decoction in delaying diabetes in rats with impaired glucose tolerance[J].International Journal of Endocrinology and Metabolism,2017,37(03):149-154.[doi:10.3760/cma.j.issn.1673-4157.2017.03.002]
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黄连解毒汤对糖耐量减低大鼠的糖尿病 延缓作用()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年03期
页码:
149-154
栏目:
论著
出版日期:
2017-05-20

文章信息/Info

Title:
Effects of huang-lian-jie-du-decoction in delaying diabetes in rats with impaired glucose tolerance
作者:
刘海逸; 张欣荣; 岳晓丹; 韩菲; 王靖宇; 杨少华; 常宝成; 杨菊红; 单春艳
300070 天津医科大学研究生院(刘海逸,张欣荣,岳晓丹,韩菲); 300070 天津医科大学代谢病医院糖尿病肾病科,卫生部激素与发育重点实验室(王靖宇,杨少华,常宝成,杨菊红,单春艳)
Author(s):
Liu Haiyi*;  Zhang Xinrong;  Yue Xiaodan;  Han Fei;  Wang Jingyu;  Yang Shaohua;  Chang Baocheng;  Yang Juhong;  Shan Chunyan.
*Graduated School of Tianjin Medical University, Tianjin 300070, China
关键词:
黄连解毒汤;  胰高血糖素样肽-1;  2型糖尿病;  肠道炎症
Keywords:
Huang-lian-jie-du-decoction;  Glucagon-like peptide-1;  Type 2 diabetes mellitus;  Intestinal inflammation
DOI:
10.3760/cma.j.issn.1673-4157.2017.03.002
摘要:
目的 观察黄连解毒汤对糖耐量减低(IGT)Zucker糖尿病肥胖(ZDF,fa/fa)大鼠糖尿病发病的延缓作用并探讨相关机制。方法 以高脂饲料诱导20只ZDF大鼠至IGT期后,将大鼠按随机数字表法分为模型组及黄连解毒汤干预组(黄连组),每组10只,并以Zucker Lean(fa/+)大鼠作为正常对照组,其中,黄连组以黄连解毒汤0.075 g/d灌胃干预,模型组及正常对照组以同体积双蒸水对照,以干预3周后,模型组全部发展至糖尿病为实验终点。行口服葡萄糖耐量试验(OGTT)观察黄连组糖尿病发病率。以酶联免疫吸附法(ELISA)测定血浆脂多糖、胰高血糖素样肽-1(GLP-1)、胰岛素及胰高血糖素(GC)水平,并以稳态模型评估-胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗; 以免疫组化方法观察不同组间回肠occludin、zonula occludens(ZO)-1、核因子-κB和肿瘤坏死因子(TNF)-α的表达。结果 药物干预3周后,模型组全部发展为糖尿病,而黄连组仅50%发展为糖尿病,且与模型组相比,黄连组空腹血糖水平(F=13.940,P<0.01)显著下降。随着糖尿病病程进展,模型组大鼠空腹血浆GC(F=51.045,P<0.01)、HOMA-IR(F=19.260,P<0.01)、脂多糖(F=10.661,P<0.05)、GLP-1(F=7.077,P<0.01)水平逐渐升高,而胰岛素(F=13.445,P<0.01)水平逐渐下降; 干预3周后,与模型组相比,黄连组胰岛素(F=1.020,P>0.05)、HOMA-IR(F=13.227,P<0.01)、GC(F=23.440,P<0.05)、脂多糖(F=22.636,P<0.01)水平均有不同程度下降,GLP-1水平升高(F=4.954,P<0.05)。在回肠,与正常对照组相比,模型组核因子-κB(F=91.951,P<0.01)和TNF-α(F=83.633,P<0.01)的表达增加,而occludin(F=105.653,P<0.01)及ZO-1(F=71.753,P<0.01)表达明显减少。黄连组上述指标均有明显改善(P均<0.01)。结论 黄连解毒汤可能通过改善GLP-1的分泌、减轻肠道炎性反应并维持肠道屏障功能,对IGT期ZDF大鼠有延缓T2DM发病的作用。
Abstract:
Objective To investigate the effects of huang-lian-jie-du-decoction in delaying diabetes in Zucker diabetes fat(ZDF, fa/fa)rats with impaired glucose tolerance(IGT)and its related mechanisms.Methods High fat diet was used to induce IGT in ZDF rats. Twenty rats were divided into model group and huang-lian-jie-du-decoction intervention group(huang-lian group)in accordance with the random number table once they entered into the stage of IGT with ten rats in each group. Zucker Lean(ZL, fa/+)rats were used as normal control group. Rats in huang-lian group were treated with huang-lian-jie-du-decoction at dose of 0.075 g/d, whereas rats in the model group and normal control group received the same volume of distilled water as vehicle. The interventions were terminated when all rats in model group developed diabetes after three weeks of intervention. Incidence of diabetes was calculated by oral glucose tolerance test(OGTT)in huang-lian group. Plasma lipopolysaccharide(LPS), glucagon-like peptide-1(GLP-1), insulin and glucagon(GC)were measured by enzyme linked immunosorbent assay(ELISA), and homeostasis model assessment of insulin resistance(HOMA-IR)index was calculated to evaluate insulin resistance. Immunohistochemistry method was used to observe the expression of occludin, zonula occludens(ZO)-1, nuclear factor-κB and tumor necrosis factor-α(TNF-α)in different groups.Results After 3 weeks of intervention, all rats in model group developed diabetes whereas only 50% rats in huang-lian group developed diabetes. And fasting blood glucose was decreased in huang-lian group compared with model group(F=13.940, P<0.01).During the progression of diabetes, the fasting plasma GC(F=51.045, P<0.01), HOMA-IR(F=19.260, P<0.01), LPS(F=10.661, P<0.05)and GLP-1 levels(F=7.077, P<0.01)of model group were gradually increased, while insulin level(F=13.445, P<0.01)was gradually decreased. After 3 weeks of treatment, compared with model group, insulin( F=1.020,P>0.05), HOMA-IR(F=13.227, P<0.01), GC(F=23.440, P<0.05)and LPS(F=22.636, P<0.01)of huang-lian group were decreased, but GLP-1 level(F=4.954, P<0.05)was increased. Compared with normal control group, the expression of nuclear factor-κB(F=91.951, P<0.01)and TNF-α(F=83.633, F<0.01)in ileum of model group were increased, and the expression of occludin(F=105.653, P<0.01)and ZO-1(F=71.753, P<0.01)in ileum decreased significantly. The above indexes were improved obviously in huang-lian group(all P<0.01).Conclusion Huang-lian-jie-du-decoction may delay the onset of type 2 diabetes in ZDF rats with IGT by improving the secretion of GLP-1, reducing intestinal inflammation and protecting the intestinal barrier function.

参考文献/References:

[1] Kappe C, Zhang Q, Nyström T, et al. Effects of high-fat diet and the anti-diabetic drug metformin on circulating GLP-1 and the relative number of intestinal L-cells[J]. Diabetol Metab Syndr, 2014,6:70. DOI: 10.1186/1758-5996-6-70.
[2] 岳峰, 许娟, 李秀莲, 等. 多囊卵巢综合征患者高糖负荷后胰高血糖素样肽1的变化[J]. 中华糖尿病杂志,2016,8(2):108-112.DOI:10.3760/cma.j.issn.1674-5809.2016.02.010.
[3] 韩瑛, 吕肖锋. 早期胰岛素泵治疗对新诊断的2型糖尿病患者血胰升血糖素样肽1的影响[J]. 中国糖尿病杂志,2011,19(2):122-124.DOI:10.3969/j.issn.1006-6187.2011.02.011.
[4] Kawanami D, Matoba K, Sango K,et al. Incretin-based therapies for diabetic complications: basic mechanisms and clinical evidence[J]. Int J Mol Sci,2016,17(8). pii: E1223. DOI: 10.3390/ijms17081223.
[5] Pang B, Zhao LH, Zhou Q,et al. Application of berberine on treating type 2 diabetes mellitus[J].Int J Endocrinol,2015,2015:905749. DOI: 10.1155/2015/905749.
[6] Yu YL, Lu SS, Yu S, et al. Huang-lian-jie-du-decoction modulates glucagon-like peptide-1 secretion in diabetic rats[J].J Ethnopharmacol,2009,124(3):444-449. DOI: 10.1016/j.jep.2009.05.027.
[7] Kawano K, Hirashima T, Mori S,et al. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty(OLETF)strain[J].Diabetes,1992,41(11):1422-1428.
[8] Soslow RA, Dannenberg AJ, Rush D,et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors[J]. Cancer, 2000,89(12):2637-2645.
[9] Tabák AG, Jokela M, Akbaraly TN,et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall Ⅱ study[J]. Lancet,2009,373(9682):2215-2221. DOI: 10.1016/S0140-6736(09)60619-X.
[10] Kemp DM. Does chronic low-grade endotoxemia define susceptibility of obese humans to insulin resistance via dietary effects on gut microbiota?[J]. Adipocyte,2013,2(3):188-190. DOI: 10.4161/adip.24776.
[11] Hameed I, Masoodi SR, Mir SA,et al. Type 2 diabetes mellitus: from a metabolic disorder to an inflammatory condition[J].World J Diabetes,2015,6(4):598-612. DOI: 10.4239/wjd.v6.i4.598.
[12] Ellingsgaard H, Hauselmann I, Schuler B,et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells[J].Nat Med,2011,17(11):1481-1489. DOI: 10.1038/nm.2513.
[13] 任泽强, 章红, 张蓬波, 等. 胃转流术对2型糖尿病大鼠胰高血糖素样肽1及小肠黏膜的影响[J]. 中华实验外科杂志,2014,31(10):2172-2174.DOI:10.3760/cma.j.issn.1001-9030.2014.10.031.
[14] 姚霜霜, 张翼飞, 张志国, 等. 小檗碱改善代谢性疾病的肠道相关机制[J]. 国际内分泌代谢杂志,2014,34(6):386-389.DOI:10.3760/cma.j.issn.1673-4157.2014.06.007.
[15] Hua W, Ding L, Chen Y,et al. Determination of berberine in human plasma by liquid chromatography-electrosprayionization-mass spectrometry[J].J Pharm Biomed Anal,2007,44(4):931-937. DOI:10.1016/j.jpba.2007.03.022.
[16] Nakajima S, Hira T, Hara H. Postprandial glucagon-like peptide-1 secretion is increased during the progressionof glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats[J].Br J Nutr,2015,113(9):1477-1488. DOI: 10.1017/S0007114515000550.
[17] 李希, 吴克芬, 任卫英, 等. 肠内营养对增龄大鼠肠黏膜上皮屏障的影响[J]. 老年医学与保健,2014,20(5):304-307.DOI:10.3969/j.issn.1008-8296.2014-09.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81473472); 天津市自然科学基金资助项目(13JCZDJC30500) 单春艳,Email:chunyanshan@hotmail.com
更新日期/Last Update: 2017-05-20