咖啡酸对高同型半胱氨酸引起的小鼠软脑膜细静脉内白细胞滚动和黏附的抑制作用

Caffeic Acid Alleviated the Leukocyte Rolling and Adhesion in Cerebral Venules Induced by Hyperhomocysteine

目的：研究咖啡酸（CA）对同型半胱氨酸（Hcy）引起的小鼠软脑膜细静脉内滚动和黏附白细胞的抑制作用。方法：取雄性C576J/BL小鼠（体重18~22g）分成3组,每组5只,Hcy组皮下注射Hcy（0.1mg/g体重）0.2ml,Hcy＋CA组皮下注射Hcy（0.1mg/g体重）0.1ml后即刻肌肉注射CA（10mg/kg体重）0.1ml,Control组皮下注射生理盐水0.2ml,4h后采用研磨法建立脑非创伤性观察窗,用动态微循环观察系统观测各组小鼠软脑膜细静脉内滚动和黏附的白细胞数量。之后取脑组织,石蜡切片,用免疫组织化学方法观察脑皮层组织中微血管内皮细胞E-选择素（E-selectin）及细胞间黏附分子-1（ICAM-1）的表达。结果：与Control组相比,Hcy组小鼠软脑膜细静脉内滚动和黏附的白细胞数量显著增加（P〈0.01）,且脑皮层微血管内皮E-selectin及ICAM-1的阳性区域也增加。Hcy＋CA组小鼠软脑膜细静脉内白细胞的滚动和黏附数量明显少于Hcy组（P〈0.05）,微血管内皮的E-selectin及ICAM-1表达也明显下调。结论：CA可以抑制Hcy引起的小鼠软脑膜细静脉内白细胞的滚动和黏附,该作用与其抑制脑微血管内皮E-selectin及ICAM-1的表达有关。

Objective: To investigate the effect of caffeic acid(CA) on leukocyte rolling and adhesion in cerebral venules induced by hyperhomocysteine(HHcy).Method: Male C576J/BL mice weighing 18~22g received Hcy(0.1 mg/g) by subcutaneous injection and subsequent intramuscular injection of CA(10 mg/kg).Four hours after injection,the leukocyte rolling and adhesion in cerebral venules was observed by intravital microscopy.Thereafter,the brain tissues were fixed,and paraffin-embedded for immunohistochemistry to determine the expression of E-selectin and ICAM-1 in cerebral venular endothelium.Results: Compared with control,Hcy injection promoted leukocyte rolling and adhesion in cerebral pial venules,as well as increased the expression of E-selectin and ICAM-1 in cerebral endothelium,all of which were alleviated by CA administration significantly.Conclusion: CA is able to inhibit Hcy-promoted leukocyte rolling and adhesion in cerebral venules,which may be related with its depression of E-selectin and ICAM-1 expression in cerebral endothelium.