黄地吉仙汤对2型糖尿病大鼠胰岛β细胞凋亡的影响
摘要
目的观察中药复方制剂黄地吉仙汤对2型糖尿病大鼠胰岛β细胞凋亡的影响,探讨具体机制。方法采用小剂量链尿佐菌素腹腔注射法制备2型糖尿病大鼠。取SD大鼠随机分为正常组、蒸馏水组、二甲双胍组和不同剂量中药组。应用中药黄地吉仙汤、二甲双胍干预,给药结束后,监测各组血糖;通过HE染色法观察大鼠胰岛形态学;通过TUNEL法、SP法测量各组胰岛细胞Bcl-2、Bax阳性细胞数和Bcl-2/Bax比率。结果与蒸馏水组比较,黄地吉仙汤组及二甲双胍组血糖均降低(P<0.05);黄地吉仙汤高、中剂量组及二甲双胍组Bcl-2阳性细胞数与蒸馏水组相比显著升高(P<0.05);蒸馏水组Bax阳性细胞数比较正常组明显偏高(P<0.05);二甲双胍组及黄地吉仙汤高、中剂量组与正常组Bax阳性细胞数显著低于蒸馏水组(P<0.05);黄地吉仙汤高、中剂量组、二甲双胍组(Bcl-2/Bax)比值比蒸馏水组明显偏高(P<0.05)。结论黄地吉仙汤可明显降低2型糖尿病大鼠血糖,减少胰岛β细胞凋亡,作用机理可能与其增强Bcl-2蛋白的表达,抑制Bax蛋白的表达,使Bcl-2/Bax比值提高有关,这可能是黄地吉仙汤影响2型糖尿病大鼠胰岛β细胞凋亡的机制之一。
引文
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[3]燕娟,郭巍伟,梁执群,等.2型糖尿病大鼠模型的建立及其验证[J].临床和实验医学杂志,2009,8(4):5-6.
[4]陈秋,夏永彭,邱宗荫.2型糖尿病大鼠模型的建立与评价[J].天津医药,2006,34(1):33-35.
[5]刘学政,萧鸿.链尿佐菌素致大鼠糖尿病模型的研究[J].锦州医学院学报,2001,22(4):11-14.
[6]Walensky LD.Bcl-2 in the crosshairs:tipping the balance of life and death[J].Cell Death Differ,2006,13(8):1339-1350.
[7]王彤,刘存志,刘玉珍,等.Bcl-2/Bax基因调控机体细胞凋亡的机制研究进展[J].中国老年学杂志,2008,28(16):1658-1660.
[8]陈灏珠,林果为,王吉耀.实用内科学[M].14版.北京:人民卫生出版社,2013:979.
[9]Skrha J.Pathogenesis of type 1 and type 2 diabetes in 2011the unifying model of glucoregulation disorder[J].Vnitr Lek,2011,57(11):949-953.
[10]Butler AE,Janson J,Bonner-Weir S,et al.Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes[J].Diabetes,2003,52(1):102-110.
[11]Farilla L,Hui H,Perfetti R.GLP-1 promoter growth and inhibit apoptosis of beta-cell in Zucker diabetic rat[J].Endocrinology,2002,143:4397-4408.
[12]Butler AE,Jang J,Gurlo T,et al.Diabetes due to a progressive defect in beta-cell mass in rats transgenic for human islet amyloid polypeptide(HIP Rat):a new model for type 2 diabetes[J].Diabetes,2004,53(6),1509-1516.
[13]田伯乐,郭志光,郝建强,等.胰岛β细胞再生与糖尿病治疗的研究进展[J].胰腺病学,2007,7(3):206-208.
[14]Brooks C,Dong Z.Regulation of mitochondrial morphological dynamics during apoptosis by Bcl-2 family proteins:a key in Bak[J].Cell Cycle,2007,6(24):3043-3047.
[15]Xie Z,Koyama T,Suzuki J,et al.Coronary reperfusion following ischemia:different expression of bcl-2 and bax proteins,and cardiomyocyte apoptosis[J].Jpn Heart J,2001,42(6):759-770.
[16]王小芳,张金盈,赵晓燕,等.二甲双胍对原代心肌细胞凋亡的影响[J].临床心血管病杂志,2013,29(4):306-308.
[17]许曼音.糖尿病学[M].2版.上海:上海科学技术出版社,2010:216.