肺腺瘤小鼠模型的建立及其血生化、血常规、尿常规、病理检测
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摘要
目的建立小鼠肺腺瘤模型并进行血生化、血常规、尿常规、病理检测。方法 PCR鉴定获得B6.129S4-Kras~(tm4Tyj/J)阳性鼠7只,4只实验组,3只对照组,另外设置3只野生型对照组,实验组和野生型对照组鼻腔滴入Cre腺病毒,每周一次,共4次。第5周取血、尿进行血生化、血常规检查,取肺组织进行病理学检测以及荧光定量PCR检测Cre表达。结果 4只阳性鼠均产生多处肺腺瘤,平均个数4.25个,体积(10.81±6.38) mm~3,对照组均未发现肿瘤。肿瘤膨胀性生长、边界清晰,瘤细胞呈立方上皮样、排列呈不规则腺管状,未见核分裂像。肺腺瘤小鼠与对照组相比低密度脂蛋白胆固醇、平均血小板体积升高,且差异有显著性;直接胆红素与对照组相比升高、高密度脂蛋白胆固醇与对照组相比降低,且差异有显著性。结论成果建立了肺肿瘤小鼠模型,并对其血生化、血常规、尿常规、病理学进行了测量。
Objective To establish a mouse model of pulmonary adenoma, detect its blood biochemistry, and routinely examine its blood, urine, and pathology. Methods PCR confirmed seven B6.129 S4-Kras~(tm4 Tyj/J-positive) mice. Four of them were used as the experimental group, and three as the control group. Three wild-type mice were used as the control group. Cre adenovirus was applied to the nasal cavity once a week for four times in both the experimental and control groups. After 5 weeks, blood and urine were collected for biochemical examination and routine blood examination. Lung tissue was analyzed for pathology, and quantitative PCR was used to detect Cre expression. Results Four positive mice produced multiple lung adenomas at an average of 4.25 with a volume of 10.81±6.38 mm~3. No tumors were found in the control group. Multiple tumors, expansive growth, and clear borders were seen in the lung. The tumor cells were cubic epidermoid and arranged in irregular glandular tubes. No pathological mitosis was seen. Compared with the control group, low-density lipoprotein and average platelet volume were increased significantly. Direct bilirubin in the pulmonary adenoma mice was higher than that in the control group, and high-density lipoprotein was lower than in the control group. These results had high statistical significance. Conclusions A mouse model of pulmonary adenoma is successfully established, and its routine examination of blood and urine,blood biochemistry parameters are determined,and its pathological features are characterized.
Objective To establish a mouse model of pulmonary adenoma, detect its blood biochemistry, and routinely examine its blood, urine, and pathology. Methods PCR confirmed seven B6.129 S4-Kras~(tm4 Tyj/J-positive) mice. Four of them were used as the experimental group, and three as the control group. Three wild-type mice were used as the control group. Cre adenovirus was applied to the nasal cavity once a week for four times in both the experimental and control groups. After 5 weeks, blood and urine were collected for biochemical examination and routine blood examination. Lung tissue was analyzed for pathology, and quantitative PCR was used to detect Cre expression. Results Four positive mice produced multiple lung adenomas at an average of 4.25 with a volume of 10.81±6.38 mm~3. No tumors were found in the control group. Multiple tumors, expansive growth, and clear borders were seen in the lung. The tumor cells were cubic epidermoid and arranged in irregular glandular tubes. No pathological mitosis was seen. Compared with the control group, low-density lipoprotein and average platelet volume were increased significantly. Direct bilirubin in the pulmonary adenoma mice was higher than that in the control group, and high-density lipoprotein was lower than in the control group. These results had high statistical significance. Conclusions A mouse model of pulmonary adenoma is successfully established, and its routine examination of blood and urine,blood biochemistry parameters are determined,and its pathological features are characterized.
引文
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[9] Catarina Rodrigues dos Santos, Isabel Fonseca Sergio Dias, et al. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression [J]. BMC Cancer, 2014, 14: 132-141.
[10] O’Malley SS, Wu R, Mayne ST, et al. Smoking cessation is followed by increases in serum bilirubin, an endogenous antioxidant associated with lower risk of lung cancer and cardiovascular disease [J]. Nicotine Tob Res, 2014, 16(8): 1145-1149.
[11] Temme EH, Zhang J, Schouten EG, et al. Serum bilirubin and 10-year mortality risk in a Belgian population [J]. Cancer Causes Control, 2001, 12(10): 887-894.
[12] Song YJ, Gao XH, Hong YQ, et al. Direct bilirubin leves are prognostic in non-small cell lung cancer [J]. Oncotarget, 2018, 9(1): 892-900.
[2] Mitsudomi T, Viallet J, Mulshine JL, et al. Mutations of ras genes distingush a subset of non-small-cell lung cancer cell lines from small-cell lung cancer cell lines [J]. Oncogene, 1991, 6(8): 1353-1362.
[3] Jackson EI, Willis N, Mercer K, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras [J]. Genes Dev, 2001, 15(24): 3243-3248.
[4] Fasbender A, Lee JH, Walters RW, et al. Incorporation of adenovirus in calcium phosphate precipitates enhances gene transfer to airway epithelia in vitro and in vivo [J]. J Clin Invest, 1998, 102(1): 184-193.
[5] Hegele RA. Plasma lipoproteins: genetic influences and clinical implications [J]. Nat Rev Genet, 2009, 10(2): 109-121.
[6] Llaverias G, Danilo C, Mercier I, et al. Role of cholesterol in the development and progression of breast cancer [J]. Am J Pathol, 2011, 178(1): 402-412.
[7] Ahn J, Lim U, Weinstein SJ, et al. Prediagnostic total and high-density lipoprotein and risk of cancer [J]. Cancer Epidemiol Biomarkers Prevention, 2009, 18(11): 2814-2821.
[8] Jafri H, Alsheikh-Ali AA, Karas RH. Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy [J]. J Am Coll Cardiol, 2010, 55(25): 2846-2854.
[9] Catarina Rodrigues dos Santos, Isabel Fonseca Sergio Dias, et al. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression [J]. BMC Cancer, 2014, 14: 132-141.
[10] O’Malley SS, Wu R, Mayne ST, et al. Smoking cessation is followed by increases in serum bilirubin, an endogenous antioxidant associated with lower risk of lung cancer and cardiovascular disease [J]. Nicotine Tob Res, 2014, 16(8): 1145-1149.
[11] Temme EH, Zhang J, Schouten EG, et al. Serum bilirubin and 10-year mortality risk in a Belgian population [J]. Cancer Causes Control, 2001, 12(10): 887-894.
[12] Song YJ, Gao XH, Hong YQ, et al. Direct bilirubin leves are prognostic in non-small cell lung cancer [J]. Oncotarget, 2018, 9(1): 892-900.