隔膜-探索淋巴管生成、退化及病理性重塑的理想组织模型
首发时间:2018-02-02
摘要:目的:分析小鼠发育与衰老过程中隔膜淋巴管网络的生成、退化及病理性重塑。 方法:利用全组织免疫荧光染色方法,分析不同年龄小鼠隔膜组织的淋巴管,展示隔膜淋巴管生成与退化的动态过程。同时结合靶向血管内皮细胞生长因子受体-3(VEGFR-3)激酶域失活性点突变的小鼠模型,分析隔膜淋巴管网络的病理性重塑。 结果:隔膜淋巴管网络形成主要发生在出生后。在出生后一天(P1)的新生鼠隔膜,可见淋巴管从背侧靠近主静脉的区域向隔膜中间生长;到P7阶段,隔膜大部分区域都覆盖有淋巴管;到P21天,淋巴管已长满整个隔膜组织。有趣的是,成年小鼠(2月龄-12月龄)阶段,隔膜中间区域的淋巴管已逐步退化;而隔膜周边区域的淋巴管密度相对于3周龄小鼠阶段也变稀。另外,尽管VEGFR-3点突变杂合小鼠的淋巴管形成受阻,但本研究发现,该突变体小鼠隔膜的部分区域有大量的淋巴管新生,详细的病理机制有待深入分析。 结论:在出生后小鼠的生长发育过程中,隔膜淋巴管经历新生与退化的变化。由于隔膜组织可进行全组织免疫组化分析,因此其可作为分析淋巴管网络再生、退化、与病理性重塑的理想组织模型,并用于开展淋巴管退化与再生分子调控机制的研究。
关键词: 隔膜 淋巴管新生 淋巴管退化 病理性淋巴管重塑 组织模型
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Diaphragm-an ideal tissue model for studying lymphatic network formation, regression, and pathological remodelling
Abstract:Purpose: Analysis of diaphragm lymphatic formation, regression and pathological remodel -ling during mouse development and aging. Method: Diaphragm lymphatic vessels were analyzed by whole-mount immunostaining at different time points. The dynamic process of diaphragm lymphatic formation and regression was visualized at time points. In addition, VEGFR-3 tyrosine kinase point mutation heterozygous mouse model was employed to show the pathological remodelling of diaphragm lymphatic vessels. Results: Diaphragm lymphatic network formation occurs mainly after birth. At postnatal day 1 (P1), diaphragm lymphatic vessels were shown to grow initially from the dorsal side near the cardinal vein. Most of the region in diaphragm was covered by lymphatic vessels at P7. By the stage of P21, lymphatic vessels covered the entire diaphragm tissue. Interestingly, in adult mice (2 month-old and 12 month-old), lymphatic vessels in the middle regions of the diaphragms have gradually regressed. Consistently, the lymphatic vessel density at the peripheral region also became sparse compared to that of P21 stage. In addition, there was little formation of diaphragm lymphatic vessels in Vegfr3 mutant mice as previously demonstrated. However, in this study, we found that intensive lymphangiogenesis was found in some regions of diaphragms of mutant mice. The pathological mechanism remains to be investigated. Conclusion: During the postnatal development, the diaphragm lymphatic vessels in mice undergo the change of formation and regression. As the diaphragm tissue can be easily analysed by whole-mount immunostaining, it is an ideal tissue model for studying the mechanism underlying lymphatic network regeneration, regression, and pathological remodeling.
Keywords: Diaphragm Lymphatic formation Lymphatic regression Pathological lymphatic remodelling Tissue model
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隔膜-探索淋巴管生成、退化及病理性重塑的理想组织模型
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