Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China.
World J Gastroenterol. 2011 Apr 7;17(13):1718-24. doi: 10.3748/wjg.v17.i13.1718.
To investigate expression of Bcl-2 and Bax in gastric ischemia-reperfusion (GI-R) and involvement of extracellular signal-regulated kinase (ERK) 1/2 activation.
The GI-R model was established by ligature of the celiac artery for 30 min and reperfusion in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 0, 0.5, 1, 3, 6, 24, 48, and 72 h. Expression and distribution of Bcl-2 and Bax proteins were analyzed by immunohistochemistry and western blotting in gastric tissue samples after sacrifice.
Compared with controls, the percentage of positive cells and protein levels of Bcl-2 decreased in the early phases of reperfusion, reached its minimum at 1 h (P < 0.05); it then increased, reaching its peak at 24 h of reperfusion (P < 0.05). The pattern of Bax expression was opposite to that of Bcl-2. Bax expression increased after reperfusion, with its peak at 1 h of reperfusion (P < 0.05), and then it decreased gradually to a minimum at 24 h after reperfusion (P < 0.05). On the other hand, inhibition of activation of ERK1/2 induced by PD98059, a specific upstream MEK inhibitor, had significant effects on Bcl-2 and Bax in GI-R. Compared with GI-R treatment only at 3 h of reperfusion, PD98059 reduced the number of Bcl-2 positive cells (0.58% of R3h group, P < 0.05) and Bcl-2 protein level (74% of R3h group, P < 0.05) but increased the number of Bax-positive cells (1.33-fold vs R3h group, P < 0.05) and Bax protein level (1.35-fold of R3h group, P < 0.05).
These results indicated that the Bcl-2 and Bax played a pivotal role in the gastric mucosal I-R injury and repair by activation of ERK1/2.
探讨细胞凋亡调控基因 Bcl-2、Bax 在胃缺血再灌注（GI-R）损伤中的表达及细胞外信号调节激酶（ERK）1/2 激活的作用。
采用夹闭大鼠腹腔动脉 30 min 后再灌注的方法制作 GI-R 模型。动物随机分为：正常对照组和再灌注 0、0.5、1、3、6、24、48、72 h 组。免疫组化和 Western blot 法检测胃组织 Bcl-2、Bax 蛋白表达和分布。
与正常对照组比较，Bcl-2 蛋白表达在再灌注早期（0.5 h）开始下降，1 h 时达最低（P < 0.05），24 h 时开始回升，72 h 时仍高于正常对照组（P < 0.05）；Bax 蛋白表达在再灌注早期（1 h）开始升高，24 h 时达高峰（P < 0.05），随后逐渐下降，72 h 时仍高于正常对照组（P < 0.05）。用 MEK 特异性抑制剂 PD98059 抑制 ERK1/2 的激活后，Bcl-2、Bax 的表达也发生相应变化。与再灌注 3 h 时单纯给予 GI-R 处理比较，PD98059 减少 Bcl-2 阳性细胞数（R3h 组的 0.58%，P < 0.05）和蛋白水平（R3h 组的 74%，P < 0.05），增加 Bax 阳性细胞数（R3h 组的 1.33 倍，P < 0.05）和蛋白水平（R3h 组的 1.35 倍，P < 0.05）。
ERK1/2 激活在调控胃黏膜 I-R 损伤与修复中可能通过调节 Bcl-2、Bax 的表达而发挥重要作用。
