噻唑烷二酮类药物对GK大鼠胰岛B细胞凋亡的影响
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Effect of rosiglitazone and pioglitazone on apoptosis of pancreatic beta-cell in GK rats
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    摘要:

    目的选择GK大鼠为2型糖尿病模型,研究噻唑烷二酮类药物(TZDs)罗格列酮和吡格列酮对胰岛B细胞保护作用的机制。方法以雄性GK大鼠和正常对照雄性Wistar大鼠为研究对象,随机分为4组:Wistar正常对照组13只(W组),GK+罗格列酮组10只(R组),GK+吡格列酮组10只(P组)和GK未治疗组10只(G组)。其中罗格列酮组给予罗格列酮钠2 mg·kg-1·d-1灌胃,吡格列酮组给予吡格列酮3 mg·kg-1·d-1灌胃,GK未治疗组不予药物干预,实验为期6周。实验结束后,取胰腺标本固定并进行电镜观察。同时采用免疫组化法检测胰岛细胞Bcl-2和Bax蛋白的表达,并采用TUNEL法检测胰腺B细胞凋亡情况。结果电镜下,G组大鼠胰岛B细胞出现核皱缩,核仁消失,染色质边集,呈现凋亡早期改变;其他3组胰岛未见凋亡改变(P<0.01)。R组和P组的Bcl-2表达显著高于G组(P<0.01);W组与G组相比差异无统计学意义。R组、P组和W组的Bax表达低于G组(P<0.05);R组和P组间差异无统计学意义。结论GK大鼠胰岛B细胞存在细胞凋亡,可能与其发生糖尿病有关。罗格列酮和吡格列酮可以减少GK大鼠胰岛B细胞凋亡,且与Bcl-2、Bax表达变化有关。

    Abstract:

    ObjectiveTo study the protective effect of two thiazolidinediones (TZDs), rosiglitazone and pioglitazoneon, on the apoptosis of pancreatic islet beta-cells. MethodsMale Goto-Kakizaki (GK) rats (a spontaneously diabetic animal model of type 2 diabetes mellitus) and non-diabetic Wistar rats were randomly divided into four groups: Wistar group (W group, n=13),GK rats fed with rosiglitazone (R group, n=10), GK rats fed with pioglitazone (P group, n=10) and GK non-treated rats(G group, n=10). Rats in R group were given rosiglitazone (2 mg·kg-1·d-1) by gavage for 6 weeks; those in A group were given pioglitazone (3 mg·kg-1·d-1) by gavage for 6 weeks. The pancreatic specimens were obtained and treated for light microscope and transmission electron microscope. Bcl-2, Bax protein expression was examined by immunohistochemistry. The apoptosis of pancreatic islet beta-cell was examined by TUNEL. ResultsThe β-cells in G group showed signs of early apoptosis: nuclei shrinkage, disappearing nucleoli, and chromatin aggregation to nuclear membrane, and the changes were not observed in the other three groups. Bcl-2 expression was significantly higher in R group and P group than in G group (P<0.01), and there was no significant difference between the W group and G group. Bax expression was significantly lower in R group, P group, and W group than in G group (P<0.05), and there was no difference between the R group and P group. ConclusionIncreased β-cells apoptosis does exist in GK rat pancreatic islets, which may contribute to the development of diabetes. Rosiglitazone and pioglitazone can prevent β-cell from apoptosis, which might be related to the changes of Bcl-2 and Bax expression.

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  • 收稿日期:2009-05-16
  • 最后修改日期:2010-04-28
  • 录用日期:2010-04-29
  • 在线发布日期: 2010-06-24
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