MMP12 缺失引起小鼠血液和白色脂肪中巨噬细胞的变化
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(1. 广东药科大学基础学院血管生物学研究所,广州 510006;2. 广东省中医院珠海分院病理科,广东珠海 519015)

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R-33

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Matrix metalloproteinase-12 knockout regulates macrophages in the blood and white fat in mice
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(1. Vascular Biology Research Institute, School of Basic Courses, Guangdong Pharmaceutical University,Guangzhou 510006, China. 2. Department of Pathology, Zhuhai Branch of Traditional Chinese Medicine Hospital of Guangdong Province, Zhuhai 519015)

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    摘要:

    目的 MMP12(matrix metalloproteinase-12)又称巨噬细胞弹性蛋白酶,几乎能分解各种细胞外基质成分和血管成分,且和单核细胞募集有关? 还发现 MMP12 参与肿瘤细胞的侵袭及转移,此外,MMP12 还与脂肪组织密切相关? 本研究旨在探讨 MMP12 敲除(MMP12- / -) 小鼠血液和白色脂肪中巨噬细胞的变化? 方法 利用PCR 对 MMP12- / -小鼠进行基因型鉴定? 用同窝 MMP12+ / +雄性小鼠做对照,检测两组小鼠的血常规并进行分析;进一步利用流式细胞术检测巨噬细胞标记物,了解巨噬细胞的变化;最后,利用免疫组化等方法来观察 MMP12 缺失后脂肪组织中巨噬细胞的变化? 结果 (1)鉴定 MMP12- / -小鼠基因型并扩群;(2)与同窝 MMP12+ / +雄性小鼠相比,MMP12- / -雄性小鼠的红细胞计数?血红蛋白量?血小板计数?单核细胞数以及其百分数等参数均下降,具有显著差异( P <0. 05);淋巴细胞百分数和嗜酸性细胞百分数,显著上升( P <0. 05),其绝对计数无统计学差异;(3)流式结果提示:巨噬细胞的特异标记物 CD11b 与 F4 / 80 双阳性细胞的比例在血液中显著下降,其绝对计数也降低;(4)H&E 染色和免疫组化的结果显示:与同窝 MMP12+ / +雄性小鼠相比,MMP12- / -雄性小鼠的白色脂肪组织中的 CD68表达明显提高? 结论 提示巨噬细胞的变化可能与 MMP12 敲除有关? 其意义在于发现 MMP12 可能调控了巨噬细胞的分化,血液中巨噬细胞减少,白色脂肪中的巨噬细胞增多?

    Abstract:

    Objective Matrix metalloproteinase-12 (MMP12) also known as macrophage elastase, is capable ofdecomposing almost all extracellular matrix components and is required for monocyte recruitment. MMP12 has been found tobe involved in cancer invasion and metastasis. In addition, MMP12 is also closely related to adipose tissue. This studyinvestigated whether MMP12 regulates the macrophages in blood and white fat in MMP12 knockout (MMP12- / -) mice.Methods MMP12- / - mice were raised and genotyped, and littermate MMP12+ / +male mice were used as controls. Theroutine blood indexes of the two groups of mice were analyzed, and the macrophage markers were detected by flowcytometry. Pathdogy using HE staining and immunohistochemistry was performed to determine the macrophages in adiposetissue after MMP12 deletion. Results (1) The genotype of MMP12- / -mice and expansion was identified. (2) Comparedwith those of littermate MMP12+ / +male mice, parameters including RBC count, HGB level, PLT count, and monocytecount and percentage were significantly reduced in MMP12- / - male mice. However, the proportions of lymphocytes andeosinophils were significantly increased compared with those of control mice, but their absolute counts did not differsignificantly. ( 3) Further result suggested that the proportion of macrophage-specific marker CD11b and F4 / 80 doublepositive cells was significantly decreased in the blood, and their absolute count was also reduced. (4) The pathdogy usingHE staining and immunohistochemistry confirmed that macrophage (CD68+) expression was significantly increased in thewhite adipose tissue of MMP12- / -male mice. Conclusions These results suggest that macrophage changes may be relatedto MMP12 knockout. The significance is that MMP12 may regulate the development of macrophages, the macrophages arereduced in the blood and increased in white fat.

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仰明明,牛婷,刘擎,张潇涵,蒋灵笔,李豪斌,王丽京,李江超. MMP12 缺失引起小鼠血液和白色脂肪中巨噬细胞的变化[J].中国比较医学杂志,2019,29(3):14~20.

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  • 收稿日期:2018-11-07
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  • 在线发布日期: 2019-04-10
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