川芎嗪对血管紧张素Ⅱ诱导的大鼠血管平滑肌细胞增殖中CaN活性及增殖细胞核抗原表达水平的影响

Effects of tetramethylpyrazine on calcinerin and proliferating cell nuclear antigen gene expression in the proliferation of vascular smooth muscle cells

目的:观察川芎嗪对血管紧张素Ⅱ(AngⅡ)诱导的血管平滑肌细胞(VSMCs)中钙调神经磷酸酶(CaN)活性及增殖细胞核抗原(PCNA)表达水平的影响。方法:建立AngⅡ诱导VSMCs增殖模型,应用免疫细胞化学法观察血管平滑肌细胞PCNA表达;并用酶促反应定磷法测定CaN活性。结果:AngⅡ组能够明显刺激VSMCs增殖,VSMCs细胞数目和细胞增殖活度明显高于正常对照组(P<0.01);CaN活性和PCNA表达量(A值)显著高于正常对照组(P<0.01)。同时加川芎嗪处理,各组CaN活性和PCNA表达水平均显著低于AngⅡ组(P<0.01)。结论:川芎嗪对AngⅡ诱导的血管平滑肌细胞增殖有显著抑制作用,其机制与抑制CaN介导的信号转导进而抑制PCNA的表达有关。

AIM： To evaluate the effects of tetramethylpyrazine （TMP） on calcineurin （CaN） and proliferating cell nuclear antigen （PCNA） gene expression in the proliferation of vascular smooth muscle cells （VSMCs） treated by angiotensin Ⅱ （ Ang Ⅱ ）. METHODS： A cell proliferating model of VSMCs induced by Ang Ⅱ was established. PCNA gene exprersion was observed by immunocytochemical staining and image analysis technique; Calcineurin （CaN） activity was detected by enzyme reaction phosphorus measurement. RESULTS： Ang Ⅱ significantly stimulated the proliferation of VSMCs, cell proliferation activity, CaN activity and the expression levels of PCAN were higher than those in control （ P 〈 0. 01 ）. While treated with TMP, the CaN activity and PCNA expression were obviously lower than those in Ang Ⅱ group （P 〈 0. 01 ）. CONCLUSION： The VSMCs proliferation induced by Angll can be inhibited by tetramethylpyrazine significantly, and the inhibiting mechanism of TMP may be related to inhibiting CaN activity and restraining the expression of PCNA in a dose and timedependent manner.