大鼠胃癌前病变形成过程中胃黏膜Sonic Hedgehog信号通路的变化

Changes of Sonic Hedgehog signaling pathway in the stomach mucosa of rats in the formation process of gastric precancerous lesions

目的:研究大鼠胃癌前病变形成过程中胃黏膜Sonic Hedgehog(Shh)信号通路的变化。方法:72只乳鼠随机分为正常组36只,造模组36只,雌雄各半。造模组灌服800 mg/L的1-甲基-3-硝基-1-亚硝基胍(MNNG)0.1 m L/d,正常组灌服生理盐水0.1 m L/d,共10 d。随后在实验观察第10周、22周、34周末每组分别雌雄各处死6只。HE染色检测胃黏膜组织病理学变化,q RTPCR法检测胃黏膜组织Shh、Ptch1、Smo、Gli1、Gli2、Gli3、Su Fu、Cyclin D1、Cyclin E1、c-Myc、β-actin m RNA的表达。Western blot检测胃黏膜组织Shh、Ptch1、Smo、Gli1、Su Fu、Cyclin D1、Cyclin E1、cMyc、p-c-Myc蛋白表达。结果:随造模时间的延长,模型组大鼠胃黏膜萎缩及异型增生逐渐加重,其胃黏膜内Shh、Smo、Gli1、Cyclin D1、Cyclin E1及c-Myc m RNA表达较正常组不同程度升高,而Ptch1和Su Fu m RNA不同程度降低。模型组胃黏膜内Shh、Smo、Gli1、Cyclin D1、Cyclin E1、p-c-Myc蛋白水平较正常组增加,Ptch1和Su Fu则降低,但差异无统计学意义。结论:大鼠胃癌前病变的形成过程中存在Shh信号通路的激活,提示Shh信号通路可能参与胃癌前病变的发生与发展。

AIM：To investigate the changes of Sonic Hedgehog signaling pathway in the stomach mucosa of rats in the formation process of gastric precancerous lesions.METHODS：Seventy-two suckling rats in half genders were randomly and equally divided into normal group and model group.The rats in the model group were given 0.1 m L MNNG at the dosage of 800 mg/L by gavage per day for 10 days,while the rats in the normal group were given normal saline.Twelve rats in each group were sacrificed at the end of the 10 th,22 th and 34 th week,respectively.Histopathologic changes of the gastric mucosa were observed by HE staining;the levels of Shh,Ptch1,Smo,Gli1,Gli2,Gli3,SuFu,Cyclin D1,Cyclin E1,c-Myc and β-actin m RNA in the gastric mucosa were determined by RealtimePCR;the expressions of Shh,Ptch1,Smo,Gli1,Su Fu,Cyclin D1,Cyclin E1,c-Myc,p-c-Myc protein were detected by Western Blot.RESULTS：With the development of the atrophy and dysplasia of gastric mucosa,the levels of Shh,Smo,Gli1,Cyclin D1,Cyclin E1 and c-Myc m RNA increased and those of Ptch1 and Su Fu m RNA decreased;the expressions of Shh,Smo,Gli1,Cyclin D1,Cyclin E1,p-c-Myc protein showed an increase trend while the expressions of Ptch1 and Su Fu protein decreased.CONCLUSION：Shh signaling is activated in the formation process of gastric precancerous lesions,which indicates Shh signaling pathway participates in the development and progression of gastric precancerous lesions.