被动吸烟对小鼠肺组织中CYP1A1、CYP1B1、VEGF和CAⅨ表达的影响
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摘要
目的探讨被动吸烟对小鼠肺组织中CYP1A1、CYP1B1、VEGF和CAⅨ表达的影响。方法利用小动物口鼻单浓度动态暴露系统构建小鼠被动吸烟模型,观察被动吸烟对小鼠体重的影响。HE染色法观察被动吸烟对小鼠肺组织结构的影响。免疫组化法检测被动吸烟对小鼠肺组织中CYP1A1、CYP1B1、VEGF和CAⅨ表达的影响。结果被动吸烟对小鼠体重影响很大,与空白对照组比较,被动吸烟不同剂量组的小鼠体重增长缓慢;HE染色结果显示:被动吸烟烟雾浓度越大,对小鼠肺组织的损伤程度越大。免疫组化结果显示:与空白对照组比较,高剂量组CYP1A1、CYP1B1、CAⅨ的阳性表达差异均有统计学意义(P <0.05);中、高剂量组VEGF的阳性表达差异有统计学意义(P <0.05)。相关性分析结果显示:高剂量组小鼠肺组织中CYP1A1与VEGF蛋白表达呈正相关(r=0.316)。结论被动吸烟对小鼠的体重影响很大;同时被动吸烟会对肺组织造成一定的损伤;并且被动吸烟能够上调小鼠肺组织CYP1A1、CYP1B1、VEGF和CAⅨ的蛋白表达,并且随着被动吸烟剂量的增加各基因的阳性表达率增加。
Objective To determine the effect of passive smoking on the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ in the lung tissue of mice. Methods Small animal mouth and nose single concentration dynamic exposure system was used to construct passive smoking mouse model and observe the influence of passive smoking on the weight of mice. HE staining was used to observe the impact of passive smoking on the structure of lung tissue in mice. Immunohistochemistry was used to detect the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ in the lung tissues of mice. Results Passive smoking had a significant influence on the weight of mice. Compared with the blank group, the weight of mice grew slowly at different passive smoking exposure doses. HE staining showed that the greater the concentration of passive smoking, the greater the damage to the lung tissues of mice. The immunohistochemistry showed that there was a significant difference in the positive expression of CYP1 A1, CYP1 B1 and CAⅨ in the high-dose group compared with the blank group(P < 0.05). Compared with the blank group, positive expression of VEGF protein in the lung tissues of the middle dose group and the high dose group had significant difference(P < 0.05). The correlation showed that the expression of CYP1 A1 and VEGF were positively correlated in the lung tissues of high dose group and the correlation coefficient was 0.316. Conclusion Passive smoking affects the weight of mice greatly, and causes certain damage to the lung tissue. Passive smoking can up-regulate the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ, and positive expression rate of each gene increases with the dose of passive smoking.
Objective To determine the effect of passive smoking on the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ in the lung tissue of mice. Methods Small animal mouth and nose single concentration dynamic exposure system was used to construct passive smoking mouse model and observe the influence of passive smoking on the weight of mice. HE staining was used to observe the impact of passive smoking on the structure of lung tissue in mice. Immunohistochemistry was used to detect the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ in the lung tissues of mice. Results Passive smoking had a significant influence on the weight of mice. Compared with the blank group, the weight of mice grew slowly at different passive smoking exposure doses. HE staining showed that the greater the concentration of passive smoking, the greater the damage to the lung tissues of mice. The immunohistochemistry showed that there was a significant difference in the positive expression of CYP1 A1, CYP1 B1 and CAⅨ in the high-dose group compared with the blank group(P < 0.05). Compared with the blank group, positive expression of VEGF protein in the lung tissues of the middle dose group and the high dose group had significant difference(P < 0.05). The correlation showed that the expression of CYP1 A1 and VEGF were positively correlated in the lung tissues of high dose group and the correlation coefficient was 0.316. Conclusion Passive smoking affects the weight of mice greatly, and causes certain damage to the lung tissue. Passive smoking can up-regulate the expression of CYP1 A1, CYP1 B1, VEGF and CAⅨ, and positive expression rate of each gene increases with the dose of passive smoking.
引文
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[14]Drenckhan A,FreytagM,SupuranCT,etal.CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target[J]. J Enzyme Inhib Med Chem,2018,33(1):1024-1033.
[15]Nardinocchi L,Puca R,Givol D,et al. HIPK2--A therapeutical target to be(re)activated for tumor suppression:Role in p53 activation and HIF-1αinhibition[J]. Cell Cycle,2010,9(7):1270-1275.
[16]Tomita S,Sinal CJ,Yim SH,et al. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator(Arnt)gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha[J]. Mol Endocrinol,2000,14(10):1674-1681.
[2]Yang G,Ibuki Y. Cigarette sidestream smoke delays nucleotide excision repair:inhibited accumulation of repair proteins at DNA lesions[J]. Carcinogenesis,2018,39(1):56-65.
[3]Masson N,Ratcliffe PJ. Hypoxia signaling pathways in cancer metabolism:the importance of co-selecting interconnected physiological pathways[J]. Cancer Metab,2014,2(1):3.
[4]Inukai T,Kaji S,Kataoka H. Analysis of nicotine and cotinine in hair by on-line in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry as biomarkers of exposure to tobacco smoke[J]. J Pharm Biomed Anal,2018,156:272-277.
[5]中华人民共和国卫生部.中国吸烟危害健康报告[M].北京:人民卫生出版社,2012.
[6]Wu Y,Song P,Zhang W,et al. Activation of AMPKα2in adipocytes is essential for nicotine-induced insulin resistance in vivo[J]. Nat Med,2015,21(4):373-382.
[7]冯一,陈丽,李红,等. FIZZ1在吸烟大鼠COPD模型肺组织的表达及与气道炎症的相关性研究[J].中国病理生理杂志,2018,34(6):1101-1108.
[8]甘桂香,胡瑞成,谭双香.吸烟COPD模型大鼠肺组织内质网相关凋亡蛋白CHOP的表达[J].中国病理生理杂志,2018,34(2):314-320.
[9]Ezzeldin N,El-Lebedy D,Darwish A,et al. Genetic polymorphisms of human cytochrome P450 CYP1A1 in an Egyptian population and tobacco-induced lung cancer[J].Genes Environ,2017,39(7):2-8.
[10]Meng FD,Ma P,Sui CG,et al. Association between cytochrome P450 1A1(CYP1A1)gene polymorphisms and the risk of renal cell carcinoma:a meta-analysis[J]. Sci Rep,2015,5:8108.
[11]Sawrycki P,Domagalski K,Cechowska M,et al. Relationship between CYP1B1 polymorphisms(c. 142C>G,c. 355G> T,c. 1294C> G)and lung cancer risk in Polish smokers[J]. Future Oncol,2018,14(16):1569-1577.
[12]Daijo H,Hoshino Y,Kai S,et al. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner[J]. Sci Rep,2016,29(6):34424.
[13]Ding G,Liu Y,Liang C,et al. Efficacy of radiotherapy on intermediate and advanced lung cancer and its effect on dynamic changes of serum vascular endothelial growth factor and matrix metalloproteinase-9[J]. Oncol Lett,2018,16(1):219-224.
[14]Drenckhan A,FreytagM,SupuranCT,etal.CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target[J]. J Enzyme Inhib Med Chem,2018,33(1):1024-1033.
[15]Nardinocchi L,Puca R,Givol D,et al. HIPK2--A therapeutical target to be(re)activated for tumor suppression:Role in p53 activation and HIF-1αinhibition[J]. Cell Cycle,2010,9(7):1270-1275.
[16]Tomita S,Sinal CJ,Yim SH,et al. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator(Arnt)gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha[J]. Mol Endocrinol,2000,14(10):1674-1681.