目的 探讨尼氟灭酸(niflumic acid,NFA)对自发性高血压大鼠(SHR)肠系膜微小动脉平滑肌细胞缝隙连接中连接蛋白43(connexin43,Cx43)表达量的影响.方法 通过尾动脉无创血压测定Wistar大鼠和SHR的血压值.应用压力肌动图检测不同浓度NFA对Wistar大鼠和SHR肠系膜微小动脉舒缩功能的影响.Western blot检测Wistar大鼠和SHR肠系膜动脉Cx43表达的差异.Western blot检测不同浓度NFA处理原代培养的SHR肠系膜微小动脉平滑肌细胞Cx43的蛋白表达水平.结果 苯肾上腺素(phenylephrine,PE)可以引起肠系膜微小动脉血管预收缩至(193±13.5) μm,而3×10-4mol/L的NFA可以使其舒张至初始水平(275±17.1) μm,且Wistar大鼠的舒张反应显著高于SHR,差异有统计学意义(F=55.47,P<0.05,n=6).SHR肠系膜动脉血管一级分支和三级分支Cx43蛋白的表达水平分别高于Wistar大鼠相应血管分支,且肠系膜三级分支血管Cx43蛋白的表达水平高于一级分支,差异有统计学意义(F=1 014.43,P<0.01).不同浓度的NFA处理的肠系膜微小动脉培养的平滑肌细胞,其Cx43蛋白的表达水平均低于对照,且呈浓度依赖性,差异有统计学意义(F=1 480.20,P<0.01).结论 Cx43可能介导了SHR肠系膜微小动脉平滑肌细胞间的通讯,从而影响血管的舒缩反应.而NFA可以降低平滑肌细胞Cx43蛋白的表达,并在一定程度上舒张血管.
Objective To explore the impact of niflumic acid (NFA) on connexin 43 (Cx43)expression in smooth muscle cells of mesenteric small artery from spontaneously hypertensive rats (SHR).Methods Blood pressure of Wistar rats and spontaneously hypertensive rats (SHR) was measured by the tail cuff method.Relaxation and contraction of mesenteric small artery from Wistar rat and SHR were evaluated by pressure myograph system under various concentrations of NFA.Protein Cx43 expression on primary cultured mesenteric smooth muscle cells from Wistar rats and SHR was detected in the absence and presence of various NFA concentrations by Western blot.Results Phenylephrine resulted in mesenteric small arteries contraction[(193 ± 13.5) μm],while NFA (3 × 10-4 mol/L) could relax the artery[(275 ±17.1) μm].The relaxation response in Wistar rats was significantly stronger than that in SHR (P <0.05).Cx43 expression of the first level branch and the third branch mesenteric artery of SHR were higher than the corresponding branch vessels of Wistar rats,and the Cx43 expression of the third branches of mesenteric artery was higher than that of the first branch (F =1 014.43,P < 0.01).Cx43 expression in primary cultured mesenteric smooth muscle cells was significantly downregulated post NFA treatment in a concentration dependent manner.Conclusion In the SHR mesenteric small arteries,Cx43 may be involved in smooth muscle cells communication,thereby affecting vascular contraction and relaxation responses.NFA could downregulate the expression of Cx43 in SHR mesenteric artery vascular smooth muscle cells and induce vasodilation.