盐酸小檗碱对糖尿病小鼠胰岛β细胞增殖与凋亡的影响  

Effect of berberine on β-cell proliferation and apoptosis in diabetes mice

作　　者：东野圣伊[1,2,3] 张惠杰[1,2,3,4] 张志国[1,2,3] 池洁[1,2,3] 占明[1,2,3] 孟祥健[1,2,3] 李博[1,2,3] 陆炎[1,2,3] 姜秀丽[1,2,3] 宁光[1,2,3] 

机构地区：[1]上海交通大学医学院附属瑞金医院内分泌代谢病科 [2]上海市内分泌代谢病研究所 [3]上海市内分泌代谢病临床医学中心,上海200025 [4]厦门大学附属第一医院糖尿病科,福建厦门361003

出　　处：《内科理论与实践》2012年第3期169-174,共6页Journal of Internal Medicine Concepts & Practice

基　　金：上海交通大学医学院博士创新基金(项目编号:BXJ201144);厦门市自然科技基金(项目编号:3502Z-20104026);福建省卫生厅青年基金(项目编号:2010-2-86)

摘　　要：目的:探讨盐酸小檗碱对2型糖尿病db/db小鼠胰岛β细胞增殖和凋亡的影响及其机制。方法:选取32只6周龄db/db雄性小鼠和32只db/m雄性小鼠,各分为2组,各选其中一组每日固定时间给予小檗碱(50 mg/kg)灌胃,另一组给予相同体积的生理盐水。连续给药3周后处死小鼠,实时荧光定量PCR和免疫组化法检测胰腺组织Ki-67、B细胞淋巴瘤/白血病2(Bcl-2)、Fas和Fas配体(Fas-L)mRNA和蛋白的表达,末端转移酶标记技术(TUNEL法)检测胰腺组织β细胞凋亡数。结果:实验3周后,小檗碱干预db/db组小鼠的血糖、葡萄糖曲线下面积显著降低,胰岛素分泌显著改善(均P<0.05)。与db/db组比较,小檗碱干预的db/db小鼠胰岛内Ki-67表达率无明显改变,差异无统计学意义(P>0.05);Bcl-2阳性表达率显著升高(P<0.01);Fas及Fas-L阳性率表达水平显著降低(P<0.01,P<0.05);β细胞凋亡率下降(P<0.01)。结论:盐酸小檗碱对促进db/db小鼠胰岛β细胞的增殖无明显作用,但是可能通过提高Bcl-2、降低Fas和Fas-L的表达来抑制凋亡,从而保护胰岛β细胞。Objective： To study the effect of bererine on β-cell proliferation and apoptosis in type 2 diabetes db/db mice. Methods： Thirty two 6-week old db/db male mice and 32 6-week old db/m male mice were divided into 2 groups respectively, and berberine [50 mg/（kg.d）] was given by gavage to one group each from db/db and db/m mice for 3 weeks, and the control groups received same volume of saline. Mice were sacrificed and Ki-67, B cell lymphoma 2 （Bcl-2）, Fas and Fas-Ligand （Fas-L） mRNA and protein expressions in pancreatic tissue were determined by real-time quantitative PCR and immunohistochemieal staining. Apoptosis of pancreatic β-eell was evaluated by terminal deoxynueleotidyl transferase dUTP nick end labeling （TUNEL） assay. Results： After 3 weeks of treatment, the blood glucose of db/dh mice treated with berberine decreased and insulin secretion improved significantly （P〈0.05） when compared with the control groups. Ki-67 expression showed no significant change （P〉O.05）, while Bcl-2 expression increased significantly （P〈0.01） and Fas and Fas-L expressions decreased significantly （P〈0.01, P〈0.05）. Theβ-cell apoptotie rate decreased markedly （P〈0.01）. Conclusions： Berberine could not promote β-cell proliferation, but it might protect pancreatic β-cells by inhibiting apoptosis via increasing the Bcl-2 and reducing the Fas and Fas-L expressions.

关 键 词：小檗碱 胰岛Β细胞 DB/DB小鼠 糖尿病 免疫组织化学 实时荧光定量PCR 凋亡 

分 类 号：R587.1[医药卫生—内分泌]