大鼠胃癌前病变形成过程中胃黏膜Sonic Hedgehog信号通路的变化

doi:10.12092/j.issn.1009-2501.2018.07.007

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (7): 761-769.doi: 10.12092/j.issn.1009-2501.2018.07.007

大鼠胃癌前病变形成过程中胃黏膜Sonic Hedgehog信号通路的变化

刘庆生¹，俞建顺²，蔡丹莉³，严茂祥⁴，王小奇⁵，桑怡⁵

¹杭州市中医院老年病科，杭州 310007，浙江；²杭州市丁桥医院消化内科，杭州 310021，浙江；³浙江省中医院重症监护室，杭州 310000，浙江；⁴浙江省中医院第二中心实验室，杭州 310000，浙江；⁵杭州市中医院消化内科，杭州 310007，浙江

收稿日期:2018-04-18 修回日期:2018-05-28 出版日期:2018-07-26 发布日期:2018-07-20
通讯作者: 刘庆生，男，主任医师，硕士研究生导师，研究方向：中医防治胃癌等病变与研究。 Tel：13858050422 E-mail：7394822@qq.com
作者简介:刘庆生，男，主任医师，硕士研究生导师，研究方向：中医防治胃癌等病变与研究。 Tel：13858050422 E-mail：7394822@qq.com
基金资助:
浙江省自然科学基金（LY13H290004）；杭州市科技计划项目（20130733Q18）；杭州市卫生科技计划重点项目（2016Z09）

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

LIU Qingsheng¹, YU Jianshun², CAI Danli³, YAN Maoxiang⁴, WANG Xiaoqi⁵, SANG Yi⁵

¹Department of Geriatrics, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang,China; ²Department of Gastroenterology, Dingqiao Hospital of Hangzhou, Hangzhou 310021, Zhejiang, China; ³Intensive Care Unit, Zhejiang Hospital of Traditional Chinese Medicine, Hangzhou 310000, Zhejiang,China;⁴ Second Central Laboratory, Zhejiang Hospital of Traditional Chinese Medicine, Hangzhou 310000, Zhejiang, China; ⁵ Department of Gastroenterology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang, China

Received:2018-04-18 Revised:2018-05-28 Online:2018-07-26 Published:2018-07-20

摘要/Abstract

摘要：

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 mL/d，正常组灌服生理盐水0.1 mL/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，qRT-PCR法检测胃黏膜组织Shh、Ptch1、Smo、Gli1、Gli2、Gli3、SuFu、CyclinD1、CyclinE1、c-Myc、β-actin mRNA的表达。Western blot检测胃黏膜组织Shh、Ptch1、Smo、Gli1、SuFu、CyclinD1、CyclinE1、c-Myc、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、CyclinD1、CyclinE1及c-Myc mRNA表达较正常组不同程度升高，而Ptch1和SuFu mRNA不同程度降低。模型组胃黏膜内Shh、Smo、Gli1、CyclinD1、CyclinE1、p-c-Myc蛋白水平较正常组增加，Ptch1和SuFu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。

关键词: 1-甲基-3-硝基-1-亚硝基胍（MNNG）, 胃癌前病变, Sonic Hedgehog信号通路

Abstract:

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 mL 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 10th, 22th and 34th week, respectively. Histopathologic changes of the gastric mucosa were observed by HE staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, CyclinD1, CyclinE1, c-Myc and β-actin mRNA in the gastric mucosa were determined by Realtime-PCR; the expressions of Shh, Ptch1, Smo, Gli1, SuFu, CyclinD1, CyclinE1, 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, CyclinD1, CyclinE1 and c-Myc mRNA increased and those of Ptch1 and SuFu mRNA decreased; the expressions of Shh, Smo, Gli1, CyclinD1, CyclinE1, p-c-Myc protein showed an increase trend while the expressions of Ptch1 and SuFu 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.

Key words: MNNG, precancerous lesions of gastric cancer, Sonic Hedgehog signaling pathway

中图分类号:

R965.2

刘庆生，俞建顺，蔡丹莉，严茂祥，王小奇，桑怡. 大鼠胃癌前病变形成过程中胃黏膜Sonic Hedgehog信号通路的变化[J]. 中国临床药理学与治疗学, 2018, 23(7): 761-769.

LIU Qingsheng, YU Jianshun, CAI Danli, YAN Maoxiang, WANG Xiaoqi, SANG Yi. Changes of Sonic Hedgehog signaling pathway in the stomach mucosa of rats in the formation process of gastric precancerous lesions[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 761-769.

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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

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