18β-甘草次酸对Wistar大鼠和自发性高血压大鼠脑微动脉平滑肌细胞缝隙连接的影响

The effect of 18β-glycyrrhetinic acid on gap junction among cerebral arteriolar smooth muscle cells in Wistar rat and spontaneously hypertensive rat

目的:本研究比较正常血压Wistar大鼠和自发性高血压大鼠(SHR)脑微动脉段平滑肌细胞电生理学及偶联力的异同,并观察18β-甘草次酸(18β-GA)对脑微动脉平滑肌细胞间缝隙连接的影响。方法:去除脑微动脉段外层结缔组织后,应用全细胞膜片钳技术,观察18β-甘草次酸对Wistar大鼠和SHR脑微动脉段上平滑肌细胞膜电容(Cinput)、膜电导(Ginput)和膜电阻(Rinput)的影响。结果:①SHR脑微动脉段上平滑肌细胞的Cinput和Ginput高于Wistar大鼠,差异有统计学意义(P<0.05)。②18β-GA可以浓度依赖性的降低脑微动脉段上平滑肌细胞的Cinput和Ginput(或者增加Rinput)。18β-GA抑制Wistar大鼠和SHR脑微动脉段上平滑肌细胞Ginput的IC50分别为1.7和2.0μmol/L,差异无统计学意义(P>0.05)。18β-GA浓度≥100μmol/L时,Wistar大鼠和SHR脑微动脉段上平滑肌细胞的Cinput、Ginput或Rinput与单个平滑肌细胞十分接近。结论:SHR脑动脉平滑肌细胞间缝隙连接耦联力增强。18β-GA可以浓度依赖抑制Wistar大鼠和SHR脑微动脉平滑肌细胞间缝隙连接,对两种大鼠的抑制效力相似。18β-GA的浓度≥100μmol/L时可以完全阻断脑微动脉平滑肌细胞间的缝隙连接。

Objective： This study compared Wistar rat with spontaneously hypertensive rat（SHR） on the electrophysiology and coupling force of the smooth muscle cells in the cerebral arteriolar segments and observe the influence of 18β-glycyrrhetinic acid（18β-GA）on the gap junctions between the arterial smooth muscle cells.Methods： The outer layer＇s connective tissue of the cerebral arteriolar segments was removed.Whole-cell patch clamp recordings were used to observe the 18β-GA＇s impaction on the arteriolar segment membrane＇s input capacitance（Cinput）,input conductance（Ginput） and input resistance（Rinput） of the smooth muscle cells.Results： ①The Cinput and Ginput of the SHR arteriolar segment smooth muscle cells was much higher than the Wistar rats,there was significant difference（P0.05）.②18β-GA concentration-dependently reduced Cinput and Ginput（or increase Rinput） on smooth muscle cells in arteriolar segment.IC50 of 18β-GA suppression＇s Ginput of the Wistar rat and SHR were 1.7 and 2.0 μmol / L respectively,there was not significant difference（P0.05）.After application of 18β-GA concentration≥100 μmol/L,the Cinput,Ginput and Rinput of the single smooth muscle cells was very close.Conclusion： Gap junctional coupling is enhanced in the SHR cerebral arterial smooth muscle cells.18β-GA concentrationdependent inhibits Wistar rat＇s and SHR cerebral arteriolar gap junctions between arterial smooth muscle cells.The inhibitory potency is similar between the two different rats.When 18β-GA concentration is ≥100 μmol/L,it can completely block gap junctions between arteriolar smooth muscle cells.