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2011;

31(6) 南方医科大学学报 (J South Med Univ) ・ 基础研究 ・ 血管内皮细胞特异性敲除cdc42 基因的杂合子小鼠与非基因敲 除小鼠在急性肺损伤肺组织病理改变以及肺微血管通透性变化 的比较 胡国栋1 , 陈英华2 , 佟万成1 , 程远雄1 , 张琳2 , 张磊2 , 蔡绍曦1 南方医科大学1 南方医院呼吸科,

2 基础医学院组织胚胎学教研室, 广东 广州

510515 摘要: 目的 比较血管内皮细胞特异性敲除cdc42基因的杂合子小鼠与非基因敲除小鼠在急性肺损伤肺组织病理改变和 肺微血管通透性变化的差异.

方法 cdc42flox/flox 小鼠与血管内皮细胞特异性表达cre重组酶的小鼠杂交, 取其基因型为 cdc42flox/+ Cre+/- 的子代小鼠与cdc42flox/flox 小鼠回交, 得到基因型分别为Cdc42flox/+ Cre+/- 、 Cdc42flox/+ Cre-/- 、 Cdc42flox/flox Cre-/- 的小 鼠, 其中Cdc42flox/+ Cre+/- 为血管内皮细胞特异性敲除cdc42基因的杂合子小鼠, 其余两种同一窝出生的非基因敲除小鼠作 为对照组, 在各组小鼠气道内滴入LPS, 制成急性肺损伤模型, 比较各组小鼠在肺组织病理改变、 病理评分、 肺湿干重比 值、 肺微血管通透系数等指标变化的差异. 结果 血管内皮细胞特异性敲除cdc42基因的杂合子小鼠急性肺损伤模型在肺 组织病理改变、 病理评分、 肺湿干重比值、 肺微血管通透系数等方面与对照组小鼠比较无明显统计学差异. 结论 血管内 皮细胞特异性敲除cdc42基因杂合子小鼠与非基因敲除小鼠比较, 在急性肺损伤中肺组织病理改变和肺微血管通透性的 变化无明显差异. 关键词: 条件性基因敲除;

cre/loxp技术;

cdc42基因;

急性肺损伤;

血管通透性 中图分类号: R563.8 文献标志码: A 文章编号: 1673-4254 (2011) 06-0995-04 The comparison between the vascular endothelial cells special cdc42-deficient heterozygous mice and the non-knockout mice on lung tissue pathological change and vasopermeability in acute lung injury HU Guo-dong1 , CHEN Ying-hua2 , TONG Wan-cheng1 , CHENG Yuan-xiong1 , ZHANG Lin2 , ZHANG Lei2 , CAI Shao-xi1

1 Department of Respiratory Disease, Nangfang Hospital,

2 Department of Histology and Embryology, Basic Medical College, Southern Medical University, Guangzhou 510515, China Abstract: Objective To compare the change of lung tissue and vasopermeability between the vascular endothelial cells special cdc42-deficient heterozygous mice and the non-knockout mice in acute lung injury. Method The mice with vascular endothelial cell-specific expression of cre recombinase were crossed with cdc42flox/flox mice. The cdc42flox/+ Cre +/- F1 offspring mice were crossed back with cdc42flox/flox mice, resulting in the F2 generation mice with three genotypes, namely cdc42flox/+ Cre +/- , cdc42flox/flox Cre-/- and cdc42flox/+ Cre +/- . The heterozygous mice with cdc42flox/+ Cre +/- genotype were selected as the model mice, with the other two genotype groups as the control. After intratracheal instillation of

2 mg/kg LPS to induce acute lung injury, the mice were sacrificed to examine the lung pathologies, lung wet/dry ratio and lung microvascular permeability. Results The heterozygous mice with cdc42 gene knockout (cdc42flox/+ Cre+/- ) showed no significant differences from the two control groups in the lung pathological score, lung wet/ dry ratio or the lung microvascular permeability coefficient. Conclusion There were no significant difference on lung tissue and vasopermeability between the vascular endothelial cells special cdc42-deficient heterozygous mice and the non-knockout mice. Key words: conditional knockout;

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