尼克酰胺转甲基酶、转化生长因子β1及Smad2在胃癌前病变中的表达

Expression of nicotinamide N-methyltransferase, transforming growth factor-β1 and Smad2 in precancerous lesions of gastric cancer

目的:探讨尼克酰胺转甲基酶(NNMT)、转化生长因子β1(TGF-β1)及Smad2在胃癌前病变(PLGC)胃黏膜组织中的表达。方法:72只SD大鼠随机数字法分为正常组和模型组,每组36只,模型组大鼠按5 ml/kg灌胃200μg/ml N-甲基-N′-硝基-N-亚硝基胍(MNNG),正常组给予等量生理盐水,造模时间8周,观察造模开始第10、22、34周大鼠胃黏膜组织变化及NNMT、TGF-β1、Smad2的表达情况,组间比较采用t检验。结果:正常组大鼠胃黏膜上皮细胞完整,腺体排列整齐,模型组随着造模时间的延长,炎性细胞浸润更加明显,腺体排列紊乱或扩张,并出现异型增生。正常组NNMT、TGF-β1、Smad2 mRNA表达量低于模型组第10天(1.00±0.10比1.37±0.13、1.00±0.10比1.32±0.12、1.00±0.10比1.29±0.13,t=5.746、5.903、5.903,P<0.01),正常组NNMT、TGF-β1、Smad2蛋白表达量低于模型组第10天(0.15±0.01比0.42±0.04、0.12±0.01比0.64±0.06、0.23±0.02比0.72±0.07,t=5.952、5.854、5.898,P<0.01)。正常组NNMT、TGF-β1、Smad2 mRNA表达量低于模型组第22天(1.00±0.10比1.67±0.13、1.00±0.10比1.62±0.16、1.00±0.10比1.59±0.16,t=5.945、6.136、6.348,P<0.01),正常组NNMT、TGF-β1、Smad2蛋白表达量低于模型组第22天(0.22±0.02比0.64±0.06、0.11±0.01比0.45±0.04、0.14±0.01比0.65±0.06,t=6.234、6.385、6.461,P<0.01)。正常组NNMT、TGF-β1、Smad2 mRNA表达量低于模型组第34天(1.00±0.10比1.86±0.19、1.00±0.10比1.82±0.18、1.00±0.10比1.76±0.17,t=6.237、6.341、6.926,P<0.01),正常组NNMT、TGF-β1、Smad2蛋白表达量低于模型组第34天(0.23±0.02比1.23±0.12、0.17±0.01比1.23±0.12、0.22±0.02比0.98±0.10,t=6.925、6.345、6.126,P<0.01)。结论:NNMT、TGF-β1及Smad2参与PLGC的发生与发展。

Objective To explore expression of Nicotinamide N-methyltransferase(NNMT),transforming growth factor-β1(TGF-β1)and Smad2 in precancerous lesions of gastric cancer(PLGC).Methods Seventy-two SD rats were divided by digital method at random into normal group and model group,each group of 36.The model group rats were given 5 ml/kg by gavage for 200μg/ml of N-methyl-N′-nitro-N-nitrosoguanidine(MNNG),the normal group was given the same amount of normal saline for 8 weeks,pathological change and the expression of NNMT,TGF-β1 and Smad2 in the gastric mucosa of rats at the 10th,22nd and 34th weeks of modeling were detected.The differences between groups were analyzed using t-test.Results In the normal group,the gastric mucosa epithelial cells were intact,the glands were arranged in order.In the model group,with the prolongation of modeling time,the infiltration of inflammatory cells became more obvious,the glands were arranged in disorder or expanded,and there was dysplasia.The expression of NNMT,TGF-β1 and Smad2 mRNA in normal group was lower than that in model group at 10th(1.00±0.10 vs.1.37±0.13,1.00±0.10 vs.1.32±0.12,1.00±0.10 vs.1.29±0.13,t=5.746,5.903,5.903,P<0.01).The expression of NNMT,TGF-β1 and Smad2 protein in normal group was lower than that in model group at 10th(0.15±0.01 vs.0.42±0.04,0.12±0.01 vs.0.64±0.06,0.23±0.02 vs.0.72±0.07,t=5.952,5.854,5.898,P<0.01).The expression of NNMT,TGF-β1 and Smad2 mRNA in normal group was lower than that in model group at 22th(1.00±0.10 vs.1.67±0.13,1.00±0.10 vs.1.62±0.16,1.00±0.10 vs.1.59±0.16,t=5.945,6.136,6.348,P<0.01).The expression of NNMT,TGF-β1 and Smad2 protein in normal group was lower than that in model group at 22th(0.22±0.02 vs.0.64±0.06,0.11±0.01 vs.0.45±0.04,0.14±0.01 vs.0.65±0.06,t=6.234,6.385,6.461,P<0.01).The expression of NNMT,TGF-β1 and Smad2 mRNA in normal group was lower than that in model group at 34th(1.00±0.10 vs.1.86±0.19,1.00±0.10 vs.1.82±0.18,1.00±0.10 vs.1.76±0.17,t=6.237,6.341,6.926,P<0.01).The expression of NNMT,TGF-β1 and Smad2 protein in normal group was lower than that in model group at 34th(0.23±0.02 vs.1.23±0.12,0.17±0.01 vs.1.23±0.12,0.22±0.02 vs.0.98±0.10,t=6.925,6.345,6.126,P<0.01).Conclusion TGF-β1 and Smad2 participated in the development and progression of PLGC.