尼氟灭酸对自发性高血压大鼠肠系膜微小动脉缝隙连接通讯的影响

Effects of niflumic acid on gap junctional intercellular communication in rat mesenteric arterioles

目的:观察尼氟灭酸(niflumic acid,NFA)对自发性高血压大鼠肠系膜微小动脉平滑肌细胞间耦联力和缝隙连接蛋白(connexin,Cx)在mRNA水平的改变。方法:应用全细胞膜片钳技术观察平滑肌细胞间耦联力的变化。不同浓度NFA孵育肠系膜微小动脉段,应用RT-PCR测定Cx37、Cx40、Cx43和Cx45在mRNA水平的改变。结果:100μmol/L NFA作用于一段血管可以降低微动脉段上平滑肌细胞的膜电容Cinput和膜电导Ginput,与对照组比较具有统计学差异(P<0.05)。不同浓度NFA处理肠系膜微小动脉,各组间Cx37的mRNA水平无显著性差异;Cx40、Cx43和Cx45的mRNA呈浓度依赖性地降低,与对照组比较具有统计学差异(P<0.01)。结论:NFA可以通过降低Cx mRNA水平调节Cx功能,抑制平滑肌细胞间的缝隙连接通讯,表明缝隙连接可能成为治疗微血管有关疾病的靶点。

Objective：To observe the effects of niflumic acid （NFA） on the coupling force between vascular smooth muscle cells （VSMCs） in spontaneously hypertensive rat mesenteric arterioles, and the changes of connex- in （Cx） mRNA level. Method： Whole-cell patch clamp recordings were used to observe the changes of the coupling force between smooth muscle cells. Different concentrations of niflumicacid treat mesenteric small arteries seg- ment, the mRNA expressions of Cx37, Cx40, Cx43, Cx45 were assayed by RT-PCR. Result： We found 100 ~tmol/L NFA in a blood vesse reduced the Cinput and Ginput of the smooth muscle cells arterial segment by whole- cell recording techniques, with the difference statistically significant （P〈0.05）. As different concentrations of ni- flumicacid treat mesenteric small arteries segment, there was no significant difference, between the mRNA expres- sions of Cx37 ; The mRNA expressions of Cx40, Cx43 and Cx45 had a concentration-dependent decrease, with the difference statistically significant （P%0.01）. Conclusion： According to the characteristics of the distribution of gap junction protein in blood vessel. It is speculated that NFA mainly inhibits the mRNA expressions of connexin of vascular smooth muscle ceils, and there is no significant effect on endothelial cells, which is used to offer theo- retical bases for gap junction targeted therapy.