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向琴,蒋宛瑾,喻嵘,吴勇军,尹业师,刘秀,苏丽清,肖凡,刘旭.白虎加人参汤对2型糖尿病小鼠肠道UCP2、AMPK表达及GLP-1分泌的影响[J].湖南中医药大学学报,2020,40(12):1444-1448[点击复制] |
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白虎加人参汤对2型糖尿病小鼠肠道UCP2、AMPK表达及GLP-1分泌的影响 |
向琴,蒋宛瑾,喻嵘,吴勇军,尹业师,刘秀,苏丽清,肖凡,刘旭 |
(湖南中医药大学, 湖南 长沙 410208;湖南科技学院, 湖南 永州 425199) |
摘要: |
目的 观察白虎加人参汤对2型糖尿病(type 2 diabetes mellitus,T2DM)MKR小鼠肠道解偶联蛋白2(uncoupling protein 2,UCP2)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)表达及胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)分泌的影响,探讨其降糖机制。方法 将MKR小鼠随机分为模型组和白虎加人参汤低、高剂量组,以FVB小鼠为空白组,中药干预4周后,观察小鼠糖代谢变化;ELISA法检测小鼠血清中胰岛素(insulin,INS)、GLP-1水平;RT-qPCR检测小鼠结肠AMPK、UCP2 mRNA水平;Western blot法检测小鼠结肠P-AMPK α、UCP2蛋白表达水平;组织形态学观察小鼠结肠组织病理形态及黏液量的变化。结果 白虎加人参汤低、高剂量组与模型组比较,均能显著降低MKR小鼠的空腹血糖和INS水平(P<0.01);并能提高血清GLP-1浓度(P<0.01,P<0.05);上调小鼠结肠AMPK mRNA和P-AMPK α水平(P<0.01),下调UCP2 mRNA和蛋白水平(P<0.01)。白虎加人参汤低、高剂量组均能明显改善MKR小鼠结肠组织病理形态。结论 白虎加人参汤可能通过抑制UCP2表达、激活AMPK的表达,促进肠道GLP-1的分泌,发挥治疗T2DM的作用。 |
关键词: 白虎加人参汤 糖尿病 肠道 胰高血糖素样肽-1 解偶联蛋白2 AMP活化蛋白激酶 |
DOI:10.3969/j.issn.1674-070X.2020.12.002 |
投稿时间:2020-09-08 |
基金项目:国家自然科学基金项目(82074400,82004185);国家重点研发计划项目(2018YFC1704300,2018YFC1704402);中医方证研究转化医学湖南省重点实验室资助(2018TP1021);湖南省自然科学基金项目(2018JJ3394);湖南省中医药科研计划项目(201931);湖南省教育厅科学研究项目(18A220,20K094,20B450);湖南中医药大学校级科研基金项目(2017-1);湖南中医药大学大学生研究性学习和创新性实验计划项目(2017-1,2019-86)。 |
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Effects of Baihu and Renshen Decoction on the Expression of UCP2, AMPK and GLP-1 Secretion in Intestinal Tract of Type 2 Diabetic Mice |
XIANG Qin,JIANG Wanjin,YU Rong,WU Yongjun,YIN Yeshi,LIU Xiu,SU Liqing,XIAO Fan,LIU Xu |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan University of Science and Engineering, Yongzhou, Hunan 425199, China) |
Abstract: |
Objective To observe the effects of Baihu and Renshen Decoction on the expression of uncoupling protein 2 (UCP2), 5'-adenosine monophosphate activated protein kinase (AMPK) and the secretion of glucagon like peptide-1 (GLP-1) in type 2 diabetes mellitus (T2DM) MKR mice, and to explore its hypoglycemic mechanism. Methods MKR diabetic mice were randomly assigned into a model group and a Baihu and Renshen Decoction low-dose and high-dose group. FVB mice were used as control group. The glucose metabolism of the mice was observed after 4 weeks of Chinese materia medica intervention. The insulin (INS) and GLP-1 levels in mice serum were detected by ELISA; The mRNA levels of AMPK and UCP2 in the colon of mice were detected by RT-qPCR. Western blot was used to detect the expression levels of P-AMPK α and UCP2 protein in the colon of mice. Morphological changes of colonic tissues and mucus quantity were observed histopathologically. Results Compared with the model group, the low and high dose groups of Baihu and Renshen Decoction could significantly reduce fasting blood glucose and INS levels in MKR mice (P<0.01), increase serum GLP-1 concentration (P<0.01, P<0.05), up-regulate the mRNA level of colonic AMPK in mice (P<0.01), and down-regulate UCP2 mRNA level (P<0.01). Meanwhile, it could up-regulate the protein expression level of colonic P-AMPK α in mice (P<0.01), and down-regulate the protein expression level of UCP2 (P<0.01). In addition, low and high dose groups of Baihu and Renshen Decoction could significantly improve colonic tissue morphology in MKR mice. Conclusion Baihu and Renshen Decoction may promote the secretion of intestinal GLP-1 and treat T2DM by inhibiting the expression of UCP2 and activating the expression of AMPK. |
Key words: Baihu and Renshen Decoction diabetes mellitus intestinal tract glucagon like peptide-1 uncoupling protein 2 5'-adenosine monophosphate activated protein kinase |
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