脑小血管平滑肌细胞表型标志及血管细胞外基质在肾性高血压大鼠中的改变

The phenotypic transition of smooth muscle cells and the change of extracellular matrix in the cerebral small vessels of renovascular hypertensive rat

目的探讨脑小血管病大鼠小动脉平滑肌细胞表型标志及细胞外基质的改变。方法随机均分12只SD大鼠,6只行双肾双夹手术建造易卒中型肾血管性高血压大鼠模型(stroke-prone renovascular hypertensive rat,RHRsp),6只为假手术组。术后7个月取脑组织,使用免疫荧光法观察脑小动脉血管平滑肌细胞表型标志物α-平滑肌肌动蛋白、平滑肌22α蛋白及细丝蛋白a改变,同时观察脑小动脉及脑小静脉血管壁基质胶原蛋白Ⅳ及层粘连蛋白的表达。结果与假手术组大鼠相比,RHRsp大鼠小动脉平滑肌细胞收缩型标志α-平滑肌肌动蛋白、平滑肌22α蛋白显著增高,合成型标志细丝蛋白a表达也显著增高。同时,RHRsp大鼠脑小动脉及脑小静脉血管壁基质胶原蛋白Ⅳ及层粘连蛋白表达均显著增高。结论 RHRsp大鼠脑小动脉平滑肌细胞收缩型标志物及合成型标志物均显著增加,提示细胞处于活跃增殖及分泌状态,导致小动脉血管管壁增厚,内径减小;脑小静脉也出现血管壁基质增生表现。

Objective To study the phenotypic transition of vascular smooth muscle cells and the change of extracellular matrix in rats with cerebral small vessel disease.Methods Two-kidney two clip surgery were adopted in 6 SD rats to build stroke-prone renovascular hypertensive rat(RHRsp).Another 6 rats were in sham-operated group.Seven months after the surgery,the brain tissues of the animals were collected.Immunofluorescence was used to observe the expression of the phenotypic markers(α-smooth muscle cells actin,smooth muscle 22αprotein and filamin a)of vascular smooth muscle cells and the extracellular matrix(collagenⅣand laminin)in the cerebral small vessels.Results Compared with rats in sham-operated group,RHRsp showed increased expression of the contractile phenotypic markers in vascular smooth muscle cells includingα-smooth muscle cells actin and smooth muscle 22αprotein.And the synthetic marker,filament a was also increased in RHRsp.Meanwhile,the expression of collagenⅣand laminin in the vascular wall matrix were significantly increased in the cerebral arterioles and cerebral venules of RHRsp.Conclusion Both contractile markers and synthetic marker of vascular smooth muscle cells in the cerebral small arteries of RHRsp rats were significantly increased,indicating that the cells were in active proliferation and secretion state,leading to thickening of the wall of the small arteries and reduction of the inner diameter.Cerebral venules in RHRsp also showed increased vascular wall matrix.