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去勢(shì)小鼠腎虛肺癌模型建立后性激素對(duì)肺癌發(fā)生的作用機(jī)制探討

發(fā)布時(shí)間:2018-08-22 20:46
【摘要】:目的:探討雄性去勢(shì)小鼠和正常小鼠Lewis肺癌移植瘤生長(zhǎng)、性激素及其受體表達(dá)的差異,了解性激素對(duì)肺癌發(fā)生的作用機(jī)制。方法 :選用24只8~9周齡C57BL/6雄性小鼠,隨機(jī)分為去勢(shì)組和對(duì)照組各12只。去勢(shì)組采用經(jīng)腹部途徑雙側(cè)睪丸切除術(shù),對(duì)照組進(jìn)行同一部位雙側(cè)睪丸周圍脂肪切除的假手術(shù)。恢復(fù)性飼養(yǎng)2周后,采用腋下皮下接種法建立小鼠Lewis肺癌模型。觀察各組小鼠體內(nèi)腫瘤的生長(zhǎng)情況,每5 d測(cè)量一次腫瘤大小。接種3周后,稱取小鼠體質(zhì)量并取血清,然后采用脫頸法處死小鼠,分別剖取移植瘤和肺組織并稱質(zhì)量。ELISA法檢測(cè)去勢(shì)組和對(duì)照組血清中雌二醇(estrodiol,E_2)和睪酮(testosterone,T)水平。免疫組織化學(xué)法檢測(cè)小鼠移植瘤與肺組織中雄激素受體(androgen receptor,AR)和雌激素受體(estrogen receptor,ER)α/β的表達(dá)情況。結(jié)果 :與對(duì)照組比較,去勢(shì)組小鼠術(shù)后體質(zhì)量減輕(P0.05),移植瘤體積增長(zhǎng)較快(P0.05),移植瘤和肺組織質(zhì)量均明顯增加(P值均0.05),肺部轉(zhuǎn)移結(jié)節(jié)數(shù)增多(P0.05),血清中E_2和T水平均成倍降低(P值均0.001)。去勢(shì)組和對(duì)照組的肺組織中,AR、ERα和ERβ均高表達(dá),且去勢(shì)組的高表達(dá)率明顯高于對(duì)照組(P值均0.05);在移植瘤組織中,去勢(shì)組和對(duì)照組的AR和ERα均低表達(dá),而ERβ高表達(dá),且去勢(shì)組的ERβ高表達(dá)率明顯高于對(duì)照組(P0.05)。結(jié)論 :去勢(shì)可引起小鼠體內(nèi)性激素水平紊亂,性激素受體表達(dá)異常上調(diào),從而使小鼠體質(zhì)量減輕,移植瘤生長(zhǎng)加速,肺部轉(zhuǎn)移結(jié)節(jié)數(shù)增多。推測(cè)性激素及其受體水平失衡可能影響肺癌的發(fā)生和發(fā)展。
[Abstract]:Objective: to investigate the difference of growth, sex hormone and its receptor expression between male ovariectomized mice and normal mice with Lewis lung cancer transplantation, and to understand the mechanism of sex hormone on lung cancer. Methods: 24 8-week old C57BL/6 mice were randomly divided into castration group (n = 12) and control group (n = 12). The ovariectomized group was treated with bilateral orchiectomy via abdominal approach, and the control group was sham-operated with bilateral peri-testicular fat resection at the same site. Lewis lung cancer model of mice was established by subaxillary subcutaneous inoculation after 2 weeks of restorative feeding. Tumor growth was observed in each group and tumor size was measured every 5 days. After 3 weeks of inoculation, the mice were weighed for body weight and serum. Then the mice were killed by neck removal method. The serum levels of estradiol E _ 2 and testosterone (testosterone T) in the ovariectomized group and the control group were detected by enzyme-linked immunosorbent assay (Elisa). The expression of androgen receptor AR and estrogen receptor ER 偽 / 尾 in transplanted tumor and lung tissue of mice were detected by immunohistochemical method. Results: compared with the control group, In ovariectomized group, the body weight decreased (P0.05), the volume of transplanted tumor increased rapidly (P0.05), the mass of transplanted tumor and lung tissue increased significantly (P < 0.05), the number of pulmonary metastatic nodules increased (P0.05), and the levels of E _ 2 and T in serum decreased exponentially (P = 0.001). The expression rate of ER 偽 and ER 尾 in castration group and control group was significantly higher than that in control group (P < 0.05), AR and ER 偽 in castration group and control group were both low, and ER 尾 expression was higher in castration group than in control group (P < 0.05). The high expression rate of ER 尾 in castration group was significantly higher than that in control group (P 0.05). Conclusion: castration can lead to disorder of sex hormone level and abnormal up-regulation of sex hormone receptor expression in mice, which can reduce the body mass, accelerate the growth of transplanted tumor and increase the number of metastatic nodules in lung. It is speculated that the imbalance of sex hormone and its receptor may affect the occurrence and development of lung cancer.
【作者單位】: 鄭州大學(xué)第一附屬醫(yī)院中西醫(yī)結(jié)合科;鄭州大學(xué)基礎(chǔ)醫(yī)學(xué)院;鄭州大學(xué)第一附屬醫(yī)院腫瘤科;鄭州大學(xué)第一附屬醫(yī)院綜合ICU;河南省腫瘤醫(yī)院(鄭州大學(xué)附屬腫瘤醫(yī)院);
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(編號(hào):81473497) 河南省科技廳社發(fā)攻關(guān)項(xiàng)目(編號(hào):132102310106) 河南省教育廳自然科學(xué)基金資助項(xiàng)目(編號(hào):12A320077)~~
【分類號(hào)】:R-332;R734.2

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