目的 探讨益气养阴活血方对2型糖尿病大鼠胰腺组织中miR-375表达水平的影响,并分析其与胰岛β细胞功能的相关性。方法 采用小剂量链脲佐菌素(STZ)加高脂饮食诱导2型糖尿病大鼠模型。设空白组、模型组、益气养阴活血方(自拟) 高、中、低剂量治疗组,于治疗8周后处死大鼠。分别测定大鼠体质量、空腹血糖(FBG)、餐后2 h血糖(2hBG)、胰岛素敏感指数(ISI)并计算胰岛素抵抗指数(HOMA-IR),胰岛素分泌指数(HOMA-β)光镜下观察胰岛形态学变化,通过实时荧光定量PCR技术检测胰腺组织中miR-375的表达水平。结果 经益气养阴活血方治疗后,大鼠的体质量、FBG、2hBG均不同程度降低(P<0.05);HOMA-IR均有所降低,ISI HOMA-β均有所升高(P<0.05);胰岛细胞形态有不同程度改善;胰腺组织中的 miR-375 表达量显著降低,模型组(2.29±0.91),益气养阴活血方低剂量组(0.33±0.21),中剂量组(0.43±0.32),高剂量组(0.48±0.19),治疗前后比较差异有统计学意义(P<0.05)。结论 益气养阴活血方可改善胰岛β细胞功能。其改善的原因可能与胰腺中miR-375表达下调有关。
Abstract
Objective To study the effect of Yi Qi Yang Yin Huo Xue decoction on miR-375 in pancreatic tissue and on the function of β cells in diabetic rat models.Methods Diabetic rat models were established using high-energy diet and intravenous injection of streptozocin(STZ).The rats were divided into blank group,model group,and high-,medium- and low-dose Yi Qi Yang Yin Huo Xue decoction groups. After 8 weeks of administration,body weight ( BW) was measured and blood was collected for detection of fasting blood glucose (FBG),fasting blood insulin(FINS),insulin sensitive index(ISI) and for calculation of the indexes of insulin resistance(HOMA-IR). Before the rats were sacrificed,2-hour plasma glucose(2hPG) was determined. The histopathological features in the islet tissue were examined with HE staining. The level of miR-375 in the islet tissue was detected with qPCR. Single factor analysis of variance was used to sort out the data.Results After the treatment with Yi Qi Yang Yin Huo Xue decoction, the levels of WB,FBG,2hPG,FINS and HOMA-IR decreased significantly (P<0.05) compared with the model group while the ISI was increased significantly(P<0.05).The islet apoptosis was reduced by the administration of this decoction.Compared with model group (2.29±0.91),the levels of miR-375 in the high dose Yi Qi Yang Yin Huo Xue decoction group(0.48±0.19),medium dose group(0.43±0.32)and low dose group(0.33±0.21)were decreased significantly(P<0.05).Conclusions Yi Qi Yang Yin Huo Xue decoction can improve islet beta cell function,and the mechanism may be associated with the down-regulation of the level of miR-375 in islet tissues.
关键词
益气养阴活血方 /
2型糖尿病大鼠 /
miR-375 /
胰岛β细胞功能
Key words
Yi Qi Yang Yin Huo Xue decoction /
T2DM model /
miR-375 /
islet beta cell function
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 高志扬,钱少平,易向明,等.2型糖尿病中医分型与B细胞功能、胰岛素敏感性的关系[J].中西医结合心脑血管杂志,2003,1(1):58.
[2] 付真真,顾经宇,郭 雯,等.利用Botnia钳夹技术评估新简易胰岛素抵抗指数在2型糖尿病患者中与胰岛素抵抗的相关性[J].南京医科大学学报(自然科学版),2013,33(5):641-645.
[3] 张翼飞,顾卫琼,晏 群,等.由血清甘油三酯和血糖所得简易指数用于评估胰岛素抵抗的临床研究[J].中华内分泌代谢杂志,2012,28(5):392-396.
[4] Yang W,Lu J,Weng J,et al.Prevalence of diabetes among men and women in China[J].N Engl J Med,2010,362(12):1090-1101.
[5] Lahmy R,Soleimani M,Sanati M H,et al. miRNA-375 promotes beta pan-creatic differentiation in human induced pluripotent stem ( hiPS ) cells[J].Molecular Biol Rep,2014,41(4):2055-2066.
[6] Nathan G,Kredo-Russo S,Geiger T,et al.MiR-375 promotes redifferentiation of adult human β cells expanded in vitro[J].PLoS One,2015,10(4):e0122108.
[7] Sun K,Chang X,Yin L,et al.Expression and DNA methylation status of microRNA-375 in patients with type 2 diabetes mellitus[J].Mol Med Rep,2014, 9(3):967-972.
[8] Lorenzo C,Wagennecht L E,D’Agostino R B Jr,et al.Insulin Resistence,bete-cell dysfunction and conversion to type 2 diabetes in a multiethnic population: the Insulin Resistence Atherosclerosis Study[J].Diabetes Care,2010,33(1):67-72.
[9] Porte D Jr,Kahn S E.β-Cell dysfunction and failure in type 2 diabetes: potential mechanisms[J].Diabetes, 2001,50( Suppl 1):S160-S163.
[10] 胥 娟,王 尧,塘 尾,等.利拉鲁肽治疗初诊断2型糖尿病患者血清miR-375的表达及胰岛功能的相关分析[J].南京医科大学学报(自然科学版),2015,35(11):1590-1593.
[11] 张 茜,肖新华,黎 明,等.天麦消渴片通过 miRNA 改善糖尿病大鼠血糖的机制[J].中国实验动物学报,2015,23(1):1-6.
[12] 杨庆宇,郜 娜.利拉鲁肽通过调节microRNA-375对胰岛细胞凋亡的影响[J].中国病理生理杂志,2016,32(9):1627-1634.
[13] Ono K,kuwabara Y,Han J.Micro RNAs and cardiovascular diseases[J].FEBS J,2011,27(8):1619-1633.
基金
河北省中医药管理局2015年度中医药类科研计划课题(2015049)
PDF(7762 KB)
