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重新恢复良好血糖控制的时机影响糖尿病大鼠视网膜中的细胞凋亡以及Bax和Bcl-2的表达。

The timing of re-institution of good blood glucose control affects apoptosis and expression of Bax and Bcl-2 in the retina of diabetic rats.

作者信息

Gao Xin-Yuan, Kuang Hong-Yu, Zou Wei, Liu Xiao-Min, Lin Hong-Bin, Yang Yi

机构信息

Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, China.

出版信息

Mol Biol Rep. 2009 Sep;36(7):1977-82. doi: 10.1007/s11033-008-9407-0. Epub 2008 Nov 8.

Abstract

Hyperglycemia initiates a sequence of events that leads to the development of diabetic retinopathy. We explored the effect of re-institution of good blood glucose control on apoptosis and apoptosis related genes (Bax and Bcl-2) in the retina of diabetic rats. Fifty male Wistar rats randomly divided into five groups : normal control group (CON), diabetic rats with high blood glucose levels for 8 months group (DM) ,diabetic rats with good blood glucose control for 8 months group (DM(1)),diabetic rats with poor blood glucose control for 2 month followed by good blood glucose control for six additional months group (DM(2)), rats with poor blood glucose control for 4 months followed by good blood glucose levels for four additional months group (DM(3)). Expression of Bax and Bcl-2 in the retina was studied by immunohistochemistry and the apoptotic cells were stained using the TUNEL method. The apoptotic cell, expression of Bax and Bcl-2 and the ratio of Bax to Bcl-2 in the retina was increased in DM group compared with normal rats' (P < 0.01). There was no significant difference in apoptotic cells and the ratio of Bax to Bcl-2 between DM(1) group and CON group. The number of TUNEL positive cells and Bax to Bcl-2 ratio was partially reversed in DM(2) group. But glucose control had no effect on the apoptotic cells and the expression of Bax and Bcl-2 in DM(3) group. There was a positive correlation between apoptotic cells and Bax/Bcl-2 ratio in the retina (r = 0.808, P < 0.01). Good blood glucose control at early stage can decrease the number of apoptotic cells in the retina; the decreased apoptosis is correlated with the down-regulation of Bax to Bcl-2 ratio.

摘要

高血糖引发一系列导致糖尿病视网膜病变的事件。我们探讨了重新良好控制血糖对糖尿病大鼠视网膜细胞凋亡及凋亡相关基因(Bax和Bcl-2)的影响。将50只雄性Wistar大鼠随机分为五组:正常对照组(CON)、血糖高水平持续8个月的糖尿病大鼠组(DM)、血糖良好控制8个月的糖尿病大鼠组(DM(1))、血糖控制不佳2个月后再良好控制6个月的糖尿病大鼠组(DM(2))、血糖控制不佳4个月后再良好控制4个月的大鼠组(DM(3))。采用免疫组织化学法研究视网膜中Bax和Bcl-2的表达,并用TUNEL法对凋亡细胞进行染色。与正常大鼠相比,DM组视网膜中的凋亡细胞、Bax和Bcl-2的表达以及Bax与Bcl-2的比值均升高(P<0.01)。DM(1)组与CON组在凋亡细胞及Bax与Bcl-2的比值方面无显著差异。DM(2)组TUNEL阳性细胞数量及Bax与Bcl-2的比值部分逆转。但血糖控制对DM(3)组的凋亡细胞及Bax和Bcl-2的表达无影响。视网膜中的凋亡细胞与Bax/Bcl-2比值呈正相关(r = 0.808,P<0.01)。早期良好的血糖控制可减少视网膜中凋亡细胞的数量;凋亡减少与Bax与Bcl-2比值的下调相关。

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