胃癌前病变大鼠胃组织GSK-3β、β-catenin及Cyclin D1的表达及意义
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摘要
目的:探讨胃癌前病变大鼠胃组织中Wnt/β-catenin信号通路相关蛋白GSK-3β、β-catenin及Cyclin D1的表达及其意义。方法:将50只SD大鼠随机分为正常组10只和模型组40只,正常组予自由饮用清洁水,进食普通颗粒饲料;模型组予150μg/m L的N-甲基-N-硝基-N-亚硝基胍(MNNG)自由饮用,同时自由进食含0.03%盐酸雷尼替丁的颗粒饲料,每4周各处死5只模型组大鼠观察造模情况,28周建立PLGC模型后处死全部大鼠。观察大鼠一般情况(体重、进食量及饮水量)及胃组织大体形态,H&E染色观察胃黏膜病理形态,免疫组织化学方法观察胃组织GSK-3β、β-catenin及Cyclin D1蛋白表达情况。结果:(1)大鼠体重及进食量、饮水量比较:与正常组比较,模型组大鼠体重、日进食量及日饮水量均有减少,具有统计学意义(P<0.05或P<0.01)。(2)病理形态学变化:正常组大鼠胃黏膜腺体形状规则、排列紧密,层次完整;模型组大鼠胃黏膜变薄,腺体减少,胃小凹粗大,或可见潘氏细胞,黏膜肌层增厚。(3)GSK-3β、β-catenin及Cyclin D1等蛋白表达情况:模型组GSK-3β于细胞质表达呈浅棕色或不着色,与正常组比较,阳性细胞平均光密度降低(P<0.05);模型组β-catenin于细胞质及细胞核呈棕色或深棕褐色、Cyclin D1于细胞核表达呈深棕褐色颗粒状,与正常组比较,阳性细胞平均光密度较正常组明显升高(P<0.01)。结论:PLGC发病与Wnt/β-catenin信号通路相关的异常激活,GSK-3β、β-catenin及Cyclin D1蛋白的异常表达有关。
Objective: To discuss the expression and significance of GSK-3β,β-catenin and Cyclin D1 which were related to Wnt/β-catenin signaling pathway in PLGC rats. Methods: Fifty rats were divided into normal group( normal drinking and feeding) and model group( drinking on 150μg/m L MNNG combined with 0. 03% ranitidine pelletized feeding). Five rats in model group were sacrificed to observe the situation of model making every 4 weeks,and all rats were sacrificed after the establishment of PLGC model in 28 weeks. We observed the general situation of the rats( weight,the daily food and drinking intake) and gross morphology of gastric mucosa in rats and observed the pathological morphology of gastric mucosa by H&E Staining. The expressions of GSK-3β,β-catenin and Cyclin D1 protein in gastric tissue were observed by immunohistochemistry. Results:(1) The weight,daily food and drinking intake of rats: Compared with the normal group,the weight,daily food intake and drinking intake of model group were all decreased significantly( P < 0. 05 or P < 0. 01).(2)Pathomorphological changes: Normal group' s rats gastric mucosal shape was normal,arranged closely and neatly. In the model group,the gastric mucosa was thinning; the glands reduced;there were the gastric pits and the propria thick or visible cells,the muscularis mucosa were thickening.(3)Expressions of GSK-3β,β-catenin and Cyclin D1: The model group's GSK-3β expression in cytoplasm and nuclear was light brown or non staining and compared with normal group,the mean optic density( MOD) was lower( P < 0. 05). The model group' s β-catenin expression in cytoplasm and nuclear was brown or dark brown. The Cyclin D1 expression in nuclear was dark brown granular. The MOD was higher significantly than that of the normal group( P < 0. 01). Conclusion: Pathogenesis of PLGC is related to the abnormal expressions of GSK-3β,β-catenin and Cyclin D1.
Objective: To discuss the expression and significance of GSK-3β,β-catenin and Cyclin D1 which were related to Wnt/β-catenin signaling pathway in PLGC rats. Methods: Fifty rats were divided into normal group( normal drinking and feeding) and model group( drinking on 150μg/m L MNNG combined with 0. 03% ranitidine pelletized feeding). Five rats in model group were sacrificed to observe the situation of model making every 4 weeks,and all rats were sacrificed after the establishment of PLGC model in 28 weeks. We observed the general situation of the rats( weight,the daily food and drinking intake) and gross morphology of gastric mucosa in rats and observed the pathological morphology of gastric mucosa by H&E Staining. The expressions of GSK-3β,β-catenin and Cyclin D1 protein in gastric tissue were observed by immunohistochemistry. Results:(1) The weight,daily food and drinking intake of rats: Compared with the normal group,the weight,daily food intake and drinking intake of model group were all decreased significantly( P < 0. 05 or P < 0. 01).(2)Pathomorphological changes: Normal group' s rats gastric mucosal shape was normal,arranged closely and neatly. In the model group,the gastric mucosa was thinning; the glands reduced;there were the gastric pits and the propria thick or visible cells,the muscularis mucosa were thickening.(3)Expressions of GSK-3β,β-catenin and Cyclin D1: The model group's GSK-3β expression in cytoplasm and nuclear was light brown or non staining and compared with normal group,the mean optic density( MOD) was lower( P < 0. 05). The model group' s β-catenin expression in cytoplasm and nuclear was brown or dark brown. The Cyclin D1 expression in nuclear was dark brown granular. The MOD was higher significantly than that of the normal group( P < 0. 01). Conclusion: Pathogenesis of PLGC is related to the abnormal expressions of GSK-3β,β-catenin and Cyclin D1.
引文
[1]Kypta RM,Waxman J.Wnt/β-catenin signalling in prostate cancer[J].Nature Reviews Urology,2012,9(8):418-428.
[2]Yu XW,Xu Q,Xu Y,et al.Expression of the E-cadherin/β-catenin/tcf-4 pathway in gastric diseases with relation to Helicobacter pylori infection:clinical and pathological implications[J].Asian Pacific journal of cancer prevention:APJCP,2014,15(1):215-220.
[3]冷秀梅,魏睦新.慢性萎缩性胃炎实验动物模型的建立和研究进展[J].世界华人消化杂志,2013,21(20):1901-1906.
[4]朱萱萱,史淋峰,吴旭彤,等.实验性慢性萎缩性胃炎脾气虚证模型的建立及不同时期病理形态学的改变[J].中华中医药学刊,2012,30(2):231-233.
[5]Kypta RM,Waxman J.Wnt/β-catenin signalling in prostate cancer[J].Nature Reviews Urology,2012,9(8):418-428.
[6]韦玉娜,覃潇,郭亚蕾,等.胃炎Ⅰ号对慢性萎缩性胃炎的疗效及其分子机制[J].中国实验方剂学杂志,2013,19(11):276-279.
[7]Van Camp JK,Beckers S,Zegers D,et al.Wnt signaling and the control of human stem cell fate[J].Stem cell reviews,2014,10(2):207-229.
[8]丁矢,郭玉凤,杜维.GSK-3β和Cyclin D1在胃癌组织中的表达及临床意义[J].肿瘤学杂志,2015,21(7):577-580.
[9]王震凯,刘炯,汪芳裕,等.β-连环蛋白和APC蛋白在胃腺瘤和胃癌中的表达及意义[J].胃肠病学和肝病学杂志,2011,20(5):404-406.
[10]王渝,赵秋,马松林,等.E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义[J].世界华人消化杂志,2007,15(4):403-407.
[11]徐晓玲,曹丽,沈琴,等.细胞周期调节蛋白D1在胆汁反流性胃炎和胃癌中的表达及其意义[J].胃肠病学,2014,19(4):235-237.
[12]曾进浩,潘华峰,刘友章,等.胃炎I号对胃癌前病变大鼠Wnt信号通路Wnt1,Wnt3a,Cyclin D1表达的影[J].中药新药与临床药理,2014,25(4):397-401.
[13]Corre P,Piazuelo MB,Camargo MC.Etiopathogenesis of gastric cancer.The future of gastric cancer prevention[J].Gastric Cancer,2004,7(1):9-16.
[2]Yu XW,Xu Q,Xu Y,et al.Expression of the E-cadherin/β-catenin/tcf-4 pathway in gastric diseases with relation to Helicobacter pylori infection:clinical and pathological implications[J].Asian Pacific journal of cancer prevention:APJCP,2014,15(1):215-220.
[3]冷秀梅,魏睦新.慢性萎缩性胃炎实验动物模型的建立和研究进展[J].世界华人消化杂志,2013,21(20):1901-1906.
[4]朱萱萱,史淋峰,吴旭彤,等.实验性慢性萎缩性胃炎脾气虚证模型的建立及不同时期病理形态学的改变[J].中华中医药学刊,2012,30(2):231-233.
[5]Kypta RM,Waxman J.Wnt/β-catenin signalling in prostate cancer[J].Nature Reviews Urology,2012,9(8):418-428.
[6]韦玉娜,覃潇,郭亚蕾,等.胃炎Ⅰ号对慢性萎缩性胃炎的疗效及其分子机制[J].中国实验方剂学杂志,2013,19(11):276-279.
[7]Van Camp JK,Beckers S,Zegers D,et al.Wnt signaling and the control of human stem cell fate[J].Stem cell reviews,2014,10(2):207-229.
[8]丁矢,郭玉凤,杜维.GSK-3β和Cyclin D1在胃癌组织中的表达及临床意义[J].肿瘤学杂志,2015,21(7):577-580.
[9]王震凯,刘炯,汪芳裕,等.β-连环蛋白和APC蛋白在胃腺瘤和胃癌中的表达及意义[J].胃肠病学和肝病学杂志,2011,20(5):404-406.
[10]王渝,赵秋,马松林,等.E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义[J].世界华人消化杂志,2007,15(4):403-407.
[11]徐晓玲,曹丽,沈琴,等.细胞周期调节蛋白D1在胆汁反流性胃炎和胃癌中的表达及其意义[J].胃肠病学,2014,19(4):235-237.
[12]曾进浩,潘华峰,刘友章,等.胃炎I号对胃癌前病变大鼠Wnt信号通路Wnt1,Wnt3a,Cyclin D1表达的影[J].中药新药与临床药理,2014,25(4):397-401.
[13]Corre P,Piazuelo MB,Camargo MC.Etiopathogenesis of gastric cancer.The future of gastric cancer prevention[J].Gastric Cancer,2004,7(1):9-16.