CAJ | 학술논문

目的：通过短暂免疫抑制，在免疫功能正常小鼠复制肺癌骨转移模型。方法6周龄雌性C57BL/6J小鼠40只，随机分为对照组（CON）、低剂量免疫抑制组（C100/D50）、中等剂量免疫抑制组（C150/D100）及高剂量免疫抑制组（C200/D150）。低剂量免疫抑制组、中等剂量免疫抑制组及高剂量免疫抑制组在实验的第1天分别腹腔注射环磷酰胺（CTX）100、150、200 mg/kg，在次日分别注射地塞米松钠（DXM）50、100、150 mg/kg，连续注射3 d。对照组小鼠腹腔注射等量生理盐水。第5天，取对数生长期的人肺腺癌A549细胞，注射1.0×109个/L浓度的细胞悬液于小鼠右后肢胫骨平台下。造模后第28天进行影像学测定并取材，评估骨质缺损程度，HE染色及免疫组织化学法观察肿瘤形态，并通过检验学指标评估骨破坏程度。结果在肿瘤注射过程中除对照组外每组各有1只死亡。试验结束时对照组小鼠全部存活；C100/D50组小鼠9只存活，仅有1只成瘤；C150/D100组小鼠存活8只，7只成瘤；C200/D150组小鼠存活4只，全部成瘤。中、高剂量免疫抑制组的小鼠体重降低明显，与其他组比较，差异有显著性意义（P<0.05）。X线及显微CT可见中、高剂量免疫抑制组小鼠胫骨平台下出现明显的骨缺损与骨破坏，其影像学表现符合肿瘤性骨破坏的改变。病理可见溶骨病变为主的混合性骨质破坏。中、高剂量免疫抑制组小鼠ALP活性明显高于其他两组，差异有显著性意义（P<0.05），但这两组间之间无明显差异。结论中、高剂量免疫抑制剂在制备小鼠肺癌骨转移模型中均具有较高的成瘤率，但中等剂量组小鼠存活率高，效果更理想。建立了比较成熟的人肺腺癌细胞移植瘤模型制备方法，为转移瘤的研究和治疗提供动物模型。
목적：통과단잠면역억제，재면역공능정상소서복제폐암골전이모형。방법6주령자성C57BL/6J소서40지，수궤분위대조조（CON）、저제량면역억제조（C100/D50）、중등제량면역억제조（C150/D100）급고제량면역억제조（C200/D150）。저제량면역억제조、중등제량면역억제조급고제량면역억제조재실험적제1천분별복강주사배린선알（CTX）100、150、200 mg/kg，재차일분별주사지새미송납（DXM）50、100、150 mg/kg，련속주사3 d。대조조소서복강주사등량생리염수。제5천，취대수생장기적인폐선암A549세포，주사1.0×109개/L농도적세포현액우소서우후지경골평태하。조모후제28천진행영상학측정병취재，평고골질결손정도，HE염색급면역조직화학법관찰종류형태，병통과검험학지표평고골파배정도。결과재종류주사과정중제대조조외매조각유1지사망。시험결속시대조조소서전부존활；C100/D50조소서9지존활，부유1지성류；C150/D100조소서존활8지，7지성류；C200/D150조소서존활4지，전부성류。중、고제량면역억제조적소서체중강저명현，여기타조비교，차이유현저성의의（P<0.05）。X선급현미CT가견중、고제량면역억제조소서경골평태하출현명현적골결손여골파배，기영상학표현부합종류성골파배적개변。병리가견용골병변위주적혼합성골질파배。중、고제량면역억제조소서ALP활성명현고우기타량조，차이유현저성의의（P<0.05），단저량조간지간무명현차이。결론중、고제량면역억제제재제비소서폐암골전이모형중균구유교고적성류솔，단중등제량조소서존활솔고，효과경이상。건립료비교성숙적인폐선암세포이식류모형제비방법，위전이류적연구화치료제공동물모형。
Objective To establish a model bearing human lung cancer xenograft with bone metastasis in mice with normal immune function. Methods Forty female C57BL/6J mice were randomly allocated into 4 equal groups, including a control group and 3 immunosuppression groups treated with low, moderate, and high doses of dexamethasone (50, 100, and 150 mg, respectively). Four days after immune suppression, the mice were subjected to percutaneous injection of1.0 × 109 L-1 A549 cells into the tibial plateau, and the bone defects were assessed radiographically 28 days after modeling. HE staining and immunohistochemical staining were used to examine the tumor tissues and bone tissue damages. Results In each of the 4 groups one mouse died during tumor cell injection. Only 1 mouse showed tumor formation in low-dose immunosuppression group, as compared to 7 and 4 in moderate- and high-dose immunosuppression groups. X-ray and microCT scan showed significant tibial bone destruction in moderate- and high-dose groups. The moderate- and high-dose groups showed similar ALP activities but both were significantly higher than those in the other two groups (P<0.05). Conclusion Immunosuppression with a moderate dose of dexamethasone results in longer survival time of the human lung cancer xenograft-bearing model mice as well as a higher tumor formation rate.