犬胆管金属支架诱导p16、p53基因扩增的实验研究

The expression of p16, p53 induced by metallic biliary stent in canine

目的探讨胆道金属支架在诱导抑癌基因扩增方面的价值。方法健康成年实验犬24只，采用经皮经肝穿刺胆囊的方法于犬胆总管下段植入支架1枚，术后正常喂养平均半年，再次麻醉后活体开腹取支架覆盖段胆管壁与支架上段胆管壁组织，通过逆转录聚合酶链反应（RT-PCR）方法检测所取组织p16、p53、p15、Bcl-2及K-ras基因的表达情况，计算两个部位胆管壁目的基因表达阳性率，采用χ2检验进行统计学分析。结果共20只实验犬建模成功。支架覆盖段胆管壁p16、p53基因表达阳性率分别为80％（16／20）、45％（9／20），支架上段胆管壁p16、p53基因表达阳性率分别为15％（3／20）、0，以上差异具有统计学意义（χ2值分别为16．94、9．17，P值均〈0．05）。支架覆盖段胆管壁p15、Bel-2、K-ras基因表达阳性率分别为60％（12／20）、100％（20／20）、0，支架上段胆管壁p15、Bcl-2、K-ras基因表达阳性率分别为70％（14／20）、100％（20／20）、0，两个部位间差异均无统计学意义（P值均〉0．05）。结论胆管壁p16、p53的扩增加强与胆道金属支架的植入有一定的相关性，对于不存在胆道支架植入禁忌证的恶性梗阻性黄疸患者建议行胆道支架植入术治疗。

Objective To explore the value of the metallic biliary stents in inducing the expression of anti-oncogenes. Methods The biliary stents were implanted in the inferior segments of CBD after a percutaneous transhepatie puncture at cholecyst in 24 dogs. After a generally observing time of half a year, the median abdominal incisions were made on the dogs under general anesthesia and the bile duct wall covered by the stents （ group Ⅰ ） and uncovered （ group Ⅱ ） were cut respectively. The expression of p16 p53 ,p15 ,Bcl-2 and K-ras in bile duct wall were detected by RT-PCR, and the positive rates of these gene expression were calculated. The differences between the two groups were analyzed by chi-spuare test for the statistics. Results The animal models were successfully set in 20 of 24 dogs. The positive rates of p16, p53 gene expression were 80% （16/20） , 45% （9/20） in the bile duct wall covered by the stents and 15% （3/20） , 0% in the bile duct wall uncovered respectively, there were significant differences between the two groups （ χ2 = 16. 94,9. 17, P 〈 0. 05 ）. The positive rates of p lS, Bel-2 and K-ras gene expression were 60% （12/20）, 100% （20/20）, 0% in the bile duct wall covered by the stents and 70% （14/20） , 100% （20/20） , 0% in the bile duct wall uncovered, there were no significant differences between the two groups （ P 〉 0. 05 ）. Conclusion The enhancement of p16, 1353 gene expression have some correlations with the implantation of metallic biliary stents. The biliary stenting is strongly recommended for the patients with malignant obstructive jaundice when no contraindications exist.