中国药理学通报2017,Vol.33Issue(8):1119-1125,7.DOI:10.3969/j.issn.1001-1978.2017.08.016
钙拮抗剂调节钙非依赖磷脂酶A2拮抗心脏微血管内皮细胞缺氧/复氧损伤的研究
Calcium antagonists protect cardiac microvascular endothelialcells against hypoxia/reoxygenation injury through iPLA2
摘要
Abstract
Aim To investigate the effects of classic calcium antagonists verapamil(Ver),nifedipine(Nif),diltiazem(Dil)and the novel calcium antagonist N-n-butyl haloperidol iodide(F2)which was synthesized by our lab by regulating Ca2+-independent phospholipase A2(iPLA2)on hypoxia/reoxygenation(H/R)injury of cardiac microvascular endothelial cells(CMECs)and the mechanisms.Methods The CMECs were isolated from SD neonatal rats.The H/R model was established,then cells were treated with different concentrations of calcium antagonists and F2.The content of LDH in the cell supernatant was measured by colorimetric method.The levels of IL-6 and AA in cell supernatant were measured by ELISA;and late-stage apoptosis was measured by TUNEL.The mRNA and protein expression levels of iPLA2 in CMECs were examined by real time-PCR and Western blot analysis.Results Calcium antagonists except Dil decreased the generation of LDH,IL-6 and AA in a dose-dependent manner(P<0.05),and reduced the apoptosis(P<0.05).F2 and Ver decreased the mRNA and protein expression of iPLA2 in a dose-dependent manner,while there were no such effects for Nif and Dil.Conclusions Calcium antagonists except Dil have protective effects against H/R injury.F2 and Ver protect CMECs against H/R injury partly through iPLA2.关键词
钙拮抗剂/碘化N-正丁基氟哌啶醇/钙非依赖磷脂酶A2/花生四烯酸/心脏微血管内皮细胞/缺氧/复氧Key words
calcium antagonist/N-n-butyl haloperidol iodide/Ca2+-independent phospholipase A2/arachidonic acid/cardiac microvascular endothelial cells/hypoxia/reoxygenation分类
医药卫生引用本文复制引用
周巧玲,王远航,林泓,汪彬,石刚刚,郑付春..钙拮抗剂调节钙非依赖磷脂酶A2拮抗心脏微血管内皮细胞缺氧/复氧损伤的研究[J].中国药理学通报,2017,33(8):1119-1125,7.基金项目
国家自然科学基金-广东联合基金资助项目(No U0932005) (No U0932005)
国家自然科学基金资助项目(No 81473215) (No 81473215)
广东省科技厅公益研究与能力建设专项资金项目(No 2014A020212290) (No 2014A020212290)