肥大细胞脱颗粒对载脂蛋白E基因敲除小鼠斑块稳定性的影响
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湖南省教育厅项目资助(10C1132)


Effects of Mast Cell Degranulation on Plaque Stabilization in Apolipoprotein E-Knock Out Mice
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    目的探讨肥大细胞脱颗粒对颈总动脉套环的载脂蛋白E基因敲除小鼠斑块稳定性的影响。方法40只雄性载脂蛋白E基因敲除小鼠予以高脂高胆固醇饲料喂养,行右颈总动脉套环术,术后4周,随机分为实验组和对照组,实验组小鼠腹腔注射肥大细胞脱颗粒剂——化合物48/80(0.5 mg/kg),对照组小鼠腹腔注射相同体积的溶媒D-Hank’s,隔日一次,共4次。第4次注射后30 min安乐死,取材。比色法测定血清类胰蛋白酶活性;甲苯胺蓝染色检测肥大细胞脱颗粒;苏木素-伊红染色观察颈总动脉病理改变及斑块内出血;Ⅷ因子相关抗原免疫组织化学染色检测斑块内新生血管密度;血管内皮钙粘蛋白、白细胞介素1β免疫组织化学染色检测其在斑块内的表达量。结果实验组套环侧颈总动脉内膜下斑块内泡沫细胞、细胞外脂质及炎性细胞较对照组明显增多;实验组肥大细胞脱颗粒、血清类胰蛋白酶活性、斑块内新生血管密度、斑块内出血、斑块内白细胞介素1β及血管内皮钙粘蛋白的表达量比对照组显著增高(P<0.05或P<0.01)。结论肥大细胞脱颗粒增加斑块内泡沫细胞、细胞外脂质及炎性细胞,并促进斑块内血管新生、斑块内出血及白细胞介素1β和血管内皮钙粘蛋白的表达,从而使斑块稳定性削弱。

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    Aim To approach the effects of mast cell degranulation on plaque stabilization in apolipoprotein E-knock out(ApoE-/-) mice with perivascular common carotid collar placement. Methods 40 male ApoE-/-mice were fed a western-type diet and operated with perivascular right common carotid collar placement.4 weeks after surgery,mice were divided into 2 groups and treated for 7 days as follows(n=20): experimental mice were intraperitoneally injected with mast cell degranulator-Compound 48/80,0.5 mg/kg;control mice were intraperitoneally injected with an equal volume of dissolvent(D-Hank's).Thirty minutes after the 4th injection,animals were sacrificed to obtain blood and carotid.Serum was collected to quantify the activity of tryptase by colorimetric assay.Sections were routinely stained with hematoxylin and eosin.Corresponding sections on separate slides were stained with toluidine blue to detect mast cell degranulation and immunohistochemically with antibodies against a von Willebrand factor(vWF),interleukin-1β(IL-1β) and VE-cadherin. Results There were more foam cells,pericellular lipids and inflammatory cells in plaque in com mon carotids with collarplacement of experimental group.The percentage of degranulated mast cells(P<0.01),the activity of tryptase in serum(P<0.05),the density of neovessel in plaque(P<0.05),intraplaque hemorrhage(P<0.05),the expressions of IL-1β(P<0.05) and VE-cadherin(P<0.05) in plaque were significantly increased in experimental group than in control group. Conclusions Mast cell degranulation increases foam cells,pericellular lipids and inflammatory cells in plaque,and promotes angiogenesis in plaque,intraplaque hemorrhage,the expressions of IL-1β and VE-cadherin in plaque,accordingly weakens plaque stabilization.

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唐雅玲, 黄韬, 王双, 许增祥, 叶旭, 孙玉慧, 杨永宗.肥大细胞脱颗粒对载脂蛋白E基因敲除小鼠斑块稳定性的影响[J].中国动脉硬化杂志,2011,19(6):469~476.

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  • 收稿日期:2010-04-21
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