本文關(guān)鍵詞：三氧化二砷降低結(jié)腸癌肺轉(zhuǎn)移小鼠調(diào)節(jié)性T細(xì)胞的實(shí)驗(yàn)研究　出處：《大連醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

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【摘要】：目的:探討三氧化二砷(arsenic trioxide,As2O3)對小鼠結(jié)腸癌肺轉(zhuǎn)移灶局部浸潤調(diào)節(jié)性T細(xì)胞(regulatory T cells,Tregs)的影響以及對腫瘤免疫微環(huán)境的調(diào)節(jié)作用。方法:1)經(jīng)尾靜脈注射CT26細(xì)胞構(gòu)建小鼠結(jié)腸癌高Tregs肺轉(zhuǎn)移模型;2)實(shí)驗(yàn)分組:對照組生理鹽水200ul/D/只,低劑量As2O3連續(xù)治療組3mg/kg/D/只,高劑量As2O3間歇治療組6mg/kg/D/只,治療2周;3)不同濃度As2O3作用于細(xì)胞因子誘導(dǎo)的殺傷性細(xì)胞(Cytokine-induced killer,CIKs),實(shí)驗(yàn)分組,對照組生理鹽水組、低濃度As2O3組0.1umol/l、中濃度As2O3組1.0umol/l、高濃度As2O3組5.0umol/l。結(jié)果:1)小鼠結(jié)腸癌肺轉(zhuǎn)移模型建模成功,3天肺部即可出現(xiàn)轉(zhuǎn)移灶,成瘤率100%;15天后,流式鑒定肺臟、脾臟Tregs與對照組相比差異顯著(p0.05);外周血Tregs無顯著性。2)體內(nèi)實(shí)驗(yàn)結(jié)果:(1)As2O3治療組能明顯提高肺轉(zhuǎn)移小鼠體重(p0.01),兩治療組之間差異顯著(p0.01);As2O3治療組顯著降低肺轉(zhuǎn)移結(jié)節(jié)數(shù)目及腫瘤負(fù)荷(p0.01),兩治療組之間差異不顯著(p0.05)。(2)As2O3治療組能顯著降低轉(zhuǎn)移肺組織中Tregs比例(p0.01),并且兩治療組之間差異顯著(p0.05)。(3)As2O3治療組能引起淋巴細(xì)胞在肺轉(zhuǎn)移小鼠體內(nèi)的重新分布,表現(xiàn)為T淋巴細(xì)胞在轉(zhuǎn)移肺中升高(p0.01)、外周血中升高(p0.01)、脾中降低(p0.01),但兩組之間差異不顯著(p0.05);3)As2O3能顯著降低CIKs中Tregs比例(p0.01),各處理組之間差異顯著(p0.05);并且能增強(qiáng)CIKs細(xì)胞體外殺傷活性,表現(xiàn)為中、高濃度組CIKs細(xì)胞毒活性顯著提高(p0.01),并且各濃度組之間差異顯著(p0.01)。結(jié)論:As2O3體外可降低CIKs中Tregs比例,提高CIKs的殺傷活性;體內(nèi)可通過降低Tregs比例、調(diào)節(jié)淋巴細(xì)胞在體內(nèi)的重新分布來發(fā)揮抗腫瘤效應(yīng)。
[Abstract]:Objective: to study arsenic trioxide (as _ 2O _ 3) arsenic trioxide. As _ 2O _ 3 (as _ 2O _ 3) could induce regulatory T cell regulatory T cells in lung metastases of colon cancer in mice. Methods mice colon cancer model with high Tregs lung metastasis was established by injecting CT26 cells via caudal vein and regulating tumor immune microenvironment. 2) the experimental group: the control group was 200 mL / D, and the low dose As2O3 group was 3 mg / kg / D / mouse. High dose As2O3 intermittent treatment group 6 mg / kg / d for 2 weeks; 3) different concentrations of As2O3 acted on cytokine-induced killer cells (Cytokine-induced kill cells). Control group, saline group, low concentration of As2O3 group 0.1 umol / L, moderate concentration of As2O3 group 1.0 umol / l. Results the lung metastasis model of mice with colon cancer and lung metastasis was successfully established for 3 days, and the tumorigenesis rate was 100%. 15 days later, compared with the control group, the Tregs of the spleen was significantly different from that of the control group (p 0.05). The results of in vivo experiment showed that the weight of mice with lung metastasis could be significantly increased in the treatment group treated with as _ 2O _ 3 (P _ (0.01)). The difference between the two groups was significant (p0.01). The number of metastatic nodules and tumor load were significantly decreased in As2O3 group (P 0.01). There was no significant difference between the two treatment groups (p0.05). The ratio of Tregs in metastatic lung tissue was significantly decreased in the treatment group (p0.01). The difference between the two treatment groups was significant (P 0.05). The treatment group could induce the redistribution of lymphocytes in mice with lung metastasis. The results showed that T lymphocytes increased p0.01 in metastatic lung, increased p0.01 in peripheral blood and decreased p0.01 in spleen, but there was no significant difference between the two groups. 3As2O3 could significantly reduce the proportion of Tregs in CIKs (p0.01), and the difference among the treatments was significant (p0.05). In addition, the cytotoxicity of CIKs cells in vitro was enhanced in the medium and high concentration groups, and the cytotoxic activity of CIKs cells was significantly increased in high concentration group (P 0.01). Conclusion: in vitro, as _ 2O _ 3 can reduce the proportion of Tregs in CIKs and increase the killing activity of CIKs. The anti-tumor effect can be played by reducing the proportion of Tregs and regulating the redistribution of lymphocytes in vivo.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.35

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