摘要
该文探究了HIF-1α/Sonic Hedgehog(Shh)信号通路的动态表达与胃黏膜病变演化过程的关系及其意义。选用72只乳鼠(SD大鼠,8周龄+,雄性)随机分为正常组、模型组,予1-甲基-3-硝基-1-亚硝基胍(N-methyl-N’-nitro-N-nitrosoguanidine,MNNG)建立胃癌前病变模型后,在第4、10、16、22、28、34周末两组分别处死6只,采用苏木精–伊红(Hematoxylin-eosin,HE)染色检测胃黏膜组织病理学变化,qRT-PCR法检测HIF-1α、VEGF、CTGF、iNOS、ET-1、Shh、Ptch1、Smo、SuFu、Gli1、Cyc-D1、Cyc-E1、c-Myc mRNA的表达,Western blot法检测HIF-1α、CTGF、iNOS、ET-1/2/3、Shh、Ptch1、Smo、SuFu、Gli-1、Cyc-D1、p-c-Myc蛋白的表达。结果显示,HE染色可见模型组大鼠胃黏膜随时间推进出现炎症、萎缩、肠化,甚至异型增生。从第28周开始,模型组大鼠胃黏膜组织内HIF-1α、VEGF、CTGF、iNOS、ET-1、Shh、Smo、Gli1、Cyc-D1、Cyc-E1 mRNA表达随造模时间增长,均有不同程度的升高,第34周时两组间的差异有统计学意义(P<0.05);SuFu mRNA表达随时间增加略呈下降趋势,差异在第34周有统计学意义(P<0.05),Ptch1 mRNA表达除16周外均呈下降趋势,但差异无统计学意义(P>0.05);模型组大鼠胃黏膜内HIF-1α、CTGF、iNOS、ET-1/2/3、Gli1蛋白表达水平呈升高趋势,28周开始组间差异有统计学意义(P<0.05),Shh、Smo、SuFu蛋白表达无明显差异(P>0.05);Ptch1蛋白表达略呈下降趋势,第4周时差异有统计学意义(P<0.05);Gli-1蛋白表达呈下降趋势,16周时差异有统计学意义(P<0.05);Cyc-D1蛋白表达在第16周有减少,差异有统计学意义(P<0.05);p-c-Myc蛋白表达呈上升趋势,第10周时差异有统计学意义(P<0.05)。这提示HIF-1α/Shh信号通路均参与胃黏膜恶性病变过程,其关键基因可作为延缓或抑制胃黏膜病变的重要靶点。
This paper aimed to study the relationship between the dynamic expression of HIF-1α/Sonic Hedgehog(Shh)signaling pathway and the evolution of gastric mucosal lesions.72 rats(SD rats,8+weeks of age,male)were randomly divided into normal group and model group.After establishing model of precancerous lesions with MNNG(N-methyl-N’-nitro-N-nitrosoguanidine),six rats in the two groups were killed respectively at the end of the 4th,10th,16th,22nd,28th and 34th week.The pathological changes of gastric mucosa were detected by HE(Hematoxylin-eosin)staining.The mRNA expressions of HIF-1α,VEGF,CTGF,iNOS,ET-1,Shh,Ptch1,Smo,SuFu,Gli1,CYC-D1,CYC-E1,and C-MYC were detected by qRT-PCR.The proteins expressions of HIF-1α,CTGF,iNOS,ET-1/2/3,Shh,Ptch1,Smo,SuFu,Gli1,CYC-D1,and P-C-MyC were detected by Western blot.The results showed that HE staining showed the gastric mucosa of the rats in the model group occurred inflammation,atrophy,intestinal meterosis,and even heterosis.From 28th weeks,the model group rats gastric mucosa tissues HIF-1α,VEGF,CTGF,iNOS,ET-1,Shh,Smo,Gli1,Cyc-D1,Cyc-E1 mRNA expression had varying degrees of growth.At 34 weeks differences between the two groups was statistically significant(P<0.05).SuFu mRNA expression showed a slightly decreasing trend with the increase of time,and the difference was statistically significant at the 34th week(P<0.05).Ptch1 mRNA expression showed a decreasing trend except for the 16th week,but the difference was not statistically significant(P>0.05).The protein expression of HIF-1α,CTGF,iNOS,ET-1/2/3,Gli-1 in the model group showed an increasing trend,and the difference between groups had statistical significance from 28 weeks(P<0.05).There were no significant differences in the protein expression of Shh,Smo and SUFU(P>0.05).The protein expression of Ptch1 showed a slightly decreasing trend,and the difference was statistically significant at the 4th week(P<0.05).The protein expression of Gli-1 showed a downward trend,and the difference was statistically significant at the 16th w
作者
钱素婷
俞建顺
邱静
陈芝芸
刘庆生
QIAN Suting;YU Jianshun;QIU Jing;CHEN Zhiyun;LIU Qingsheng(Guangxing Hospital affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,China;Department of Gastroenterology,Dingqiao Hospital of Hangzhou,Hangzhou 310021,China;The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China;Department of Geriatrics,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2021年第5期1012-1020,共9页
Chinese Journal of Cell Biology
基金
浙江省自然科学基金(批准号:LY13H290004)
杭州市科技计划项目(批准号:20130733Q18)
杭州市医药卫生科技计划重点项目(批准号:2016Z09)资助的课题。
关键词
HIF-1α/Shh信号通路
胃黏膜病变
胃癌前病变
HIF-1α/Shh signaling pathway
gastric mucosal lesions
precancerous lesions of gastric cancer
