凋亡相关蛋白Bcl-2、Bax在消炎痛所致胃黏膜细胞凋亡中的作用  

Role of apoptosis-associated protein Bcl-2 and Bax in indomethacin-induced gastric mucosal cell apoptosis

作　　者：崔忠敏[1] 李兆申[2] 

机构地区：[1]沈阳沈阳军区总医院消化内科,110840 [2]上海长海医院消化内科,200433

出　　处：《现代消化及介入诊疗》2012年第1期12-15,共4页Modern Interventional Diagnosis and Treatment in Gastroenterology

摘　　要：目的研究在体情况下消炎痛(Indomethacin,IND)所致胃黏膜细胞凋亡过程中Bcl-2、Bax蛋白表达的变化,以探讨其黏膜损伤机制。方法 SD大鼠胃内灌注不同剂量IND,灌胃后3h处死,采用TUNEL标记技术检测黏膜细胞凋亡;应用免疫组化方法检测Bcl-2、Bax蛋白表达的变化。结果①TUNEL标记显示对照组大鼠胃黏膜仅见少量凋亡细胞,IND使凋亡细胞数明显增加,计算机图像分析显示单位面积内阳性细胞平均像素点30mg/kg组为对照组的6.3倍(P<0.01),60～120mg/kg组分别为对照组的8.0、12.6和17.1倍,明显高于对照组(P<0.01);②免疫组化染色显示对照组大鼠Bcl-2在胃腺体部呈中等至强阳性表达,平均灰度值为113.8±9.6;而Bax蛋白仅在胃腺体及基底部呈弱阳性表达,平均灰度值为128.5±6.1。30mg/kgIND使Bcl-2表达明显减弱(P<0.05vs对照组),灰度值为124.8±6.3,60～90mg/kg组呈中等至弱阳性表达,灰度值分别为153.1±10.1、174.1±8.6,120mg/kg组仅见散在弱阳性细胞分布于胃腺体部,灰度值为222.3±14.6,表达均明显低于对照组(P<0.01),表达水平变化同细胞凋亡显著负相关(r=-0.9771,P<0.01);Bax表达在30～90mg/kg组呈中等阳性,明显高于对照组(P<0.05),灰度值分别为107.4±4.2、90.1±5.6、72.8±6.3,120mg/kg组在胃腺体及基底部见大量强阳性染色细胞分布,灰度值为69.8±6.2,表达明显高于对照组(P<0.01),其变化与细胞凋亡明显正相关(r=0.9725,P<0.01)。结论 IND使凋亡抑制蛋白Bcl-2表达减弱和促凋亡蛋白Bax表达增强,从而降低了Bcl-2/Bax,导致胃黏膜细胞凋亡。Objective To determine the changing expressions of Bcl-2 and Bax protein during indomethacin （IND）-induced gastric mucosal cell apoptosis in vivo. Methods Healthy male Sprague-Dawley rats were treated intragastrically with four different doses of IND. The rats were killed 3 hours after IND ad- ministration and the TUNEL technique was applied to detect mucosal cell apoptosis. The changes of Bcl-2 and Bax protein expression were monitored immunohistochemically. Results TUNEL assay revealed only a few apoptotic cells in rats in control group. Oral administration of 1ND resulted in the appearance of massive TUN-EL positive cells. Computer-aided image analysis showed the mean pixels in 30 - 120 mg/kg groups were 6.3-, 8.0-, 12.6- and 17.1-folds that in control group （P 〈 0.01 vs control）. In rats of control group, immuno histochemistry showed that Bcl-2 protein was moderate to strong positive in the middle portion of gastric glands. The mean gray level was 113.8 ± 9.6. In contrast, Bax protein was detected only as a weak signal in the basal and body regions of gastric glands, and the mean gray level was 128.5 ± 6.1. IND administration caused a significant decrease in Bcl-2 expression in a dose-dependent manner. The mean gray level in 30mg/kg group was 124.8 ± 6.3 （P 〈 0.05 vs control）. The positive signals in 60 - 90 mg/kg groups were moderate to weak, being significantly lower than that in control group （153.1 ± 10.1, 174.1 ± 8.6, P 〈 0.01）. In 120 mg/kg group, only a few scattered positive cells were seen in the body region of gastric glands （222.3 ± 14.6, P 〈 0.01 vs control）. The change of Bcl-2 expression was significantly negative-related with mucosal cell apoptosis （r = - 0.9771, P 〈 0.01）. The expression of Bax protein was significantly enhanced by IND treatment dose-depen- dently. In 30 - 90 mg/kg groups, the positive signals were weak to moderate （107.4 ± 4.2, 90.1 ± 5.6, 72.8 ± 6.3, P 〈 0.05 vs control）. In rats treated with IND at the dose of 120 mg/kg, mass

关 键 词：消炎痛 胃黏膜 细胞凋亡 BCL-2 BAX 

分 类 号：R979.1[医药卫生—药品]