三七皂苷R1对肺高压大鼠肺动脉平滑肌细胞SOCE的抑制作用

摘要

目的：探讨三七皂苷R1(notoginsenoside R1)对慢性低氧(chronic hypoxia, CH)及野百合碱(monocrotaline, MCT)致肺高压( pulmonary hypertension,PH)大鼠肺动脉平滑肌细胞( pulmonary arterial smooth muscle cells, PASMCs)钙池操纵性钙内流( store-operated calcium entry, SOCE)的作用。方法制备CH及MCT致PH大鼠模型,通过Mn2+淬灭Fura-2荧光和Fluo-3荧光检测胞质游离Ca2+浓度( intracellular free calcium concentration,[ Ca2+] i )观察三七皂苷R1对CH及MCT致 PH大鼠 PASMCs SOCE的作用。结果成功制备CH及MCT致PH大鼠模型；在硝苯地平预处理情况下,10μmol·L-1三七皂苷 R1可明显降低环匹阿尼酸( cyclopia-zonic acid,CPA)诱导CH及MCT致PH大鼠PASMCs Mn2+淬灭幅度、Mn2+最大淬灭率、胞膜 Ca2+内流量和静息[ Ca2+] i。结论三七皂苷 R1对 CH 及 MCT 致 PH 大鼠PASMCs具有抑制 SOCE和降低静息[ Ca2+] i 的作用。%Aim To evaluate the effects of notoginsen-oside R1 on store-operated calcium entry ( SOCE ) in pulmonary arterial smooth muscle cells ( PASMCs ) of chronic hypoxia ( CH)-and monocrotaline ( MCT)-in-duced pulmonary hypertension ( PH) rats. Methods Mn2+ quenching of Fura-2 and measurement of intra-cellular free calcium concentration ( [ Ca2+] i ) using fluo-3 were examined in PASMCs of CH-exposed and MCT-treated rats. Results ①CH-exposed and MCT-treated rats exhibited profound PH when examined 3 weeks after hypoxia exposure or MCT injection, respec-tively. ②In the presence of 3 μmol·L-1 nifedipine, 10 μmol · L-1 notoginsenoside R1 significantly re-duced cyclopiazonic acid ( CPA )-induced the percent reduction in Fura-2 fluorescence measured 500 sec af-ter application of Mn2+, the maximal rate of Mn2+quenching, the amplitude of the Ca2+ influx transient and the resting [ Ca2+] i in PASMCs of CH-exposed and MCT-treated rats. Conclusion Notoginsenoside R1 inhibits SOCE and reduces resting [ Ca2+] i in PASMCs of CH-and MCT-induced PH rats.