TRPV4在小鼠脑血管内皮细胞中的表达及对血管张力调节作用研究

Expression profile of TRPV4 in mouse brain vascular endothelial cells and its regulatory effect on vessel tension

目的比较瞬时受体电位(TRP)通道家族中香草素受体亚家族(TRPV)和经典瞬时感受器电位亚家族(TRPC)在小鼠脑、心和肝微血管内皮细胞表达差异,寻找脑微血管中具有特异性高表达亚型,阐明其对脑动脉血管舒张的调节作用。方法挖掘GEO数据库中芯片表达谱数据,分析各个通道亚型差异表达情况,再采用免疫组化检测TRPV4、TRPP2和TRPC1在脑基底动脉中表达情况,血管张力实验检测TRPV4通道在调节小鼠脑基底动脉舒张中的效应。结果通过分析表达谱数据显示,在小鼠脑、心和肝三种微血管内皮中,TRPV4通道在脑微血管内皮细胞显著高表达,而TRPC3通道显著低表达。TRPV4、TRPP2和TRPC1在脑基底动脉内皮和平滑肌层也显著表达。TRPV4通道激动剂GSK1016790A能浓度依赖地舒张苯肾上腺素引起的脑基底动脉收缩,而且其舒张效应可以被TRPV4通道阻断剂HC067047所阻断。结论与心和肝血管内皮细胞相比,TRPV4通道在小鼠脑血管内皮细胞中显著高表达,可能在调节脑血管内皮功能中具有重要意义。

Objective To compare the expression difference of transient receptor potential subfamilies including transient receptor potential vanilloid（TRPV） and transient receptor potential canonical（ TRPC ） channels in mouse microvascular endothelial cells from brain, heart and liver, and find a specific high expression subtypes in brain microvessels endothelial cells, to clarify its regulation function in cerebral vasodilatation. Methods The array data for the expression profiling from GEO Databases was analyzed to clarify the expression profiles of all TRPV and TR- PC channel subtypes. Then immunohistochemistry was used to identify the expression profile of TRPV4, TRPP2 and TRPC1 in the cerebral basilar artery, and vessel tension measurement was used to investigate the regulatory effect of TRPV4 channel having high expression level on the cerebral basilar artery relaxation. Results The results showed that in three types of endothelial cells from brain, heart and liver, the expression level of TRPV4 channel was highest but the expression level of TRPC3 was lowest in brain microvascular endothelial cells. TRPV4, TRPP2 and TRPC1 were expressed in the endothelial and smooth muscle layers of the cerebral basilar artery as well. GSK1016790A, an agonist of TRPV4, concentration-dependently relaxed the cerebral basilar artery which was pre- constructed by phenylephrine. Additionally, GSK1016790A-induced vessel relaxation was inhibited by HC067047, an antagonist of TRPV4. Conclusion Compared with the microvascular endothelial cells from heart and liver, the brain microvascular endothelial cells show significantly high expression in TRPV4 channel. Therefore, TRPV4 may have a critical role in the function of brain microvascular endothelial ceils.