中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2011年
4期
348-352
,共5页
王如兴%李库林%张常莹%郑杰%郭素峡%吴(王莹)%李肖蓉%柴强%陆彤%LEE Hon-chi
王如興%李庫林%張常瑩%鄭傑%郭素峽%吳(王瑩)%李肖蓉%柴彊%陸彤%LEE Hon-chi
왕여흥%리고림%장상형%정걸%곽소협%오(왕형)%리초용%시강%륙동%LEE Hon-chi
冠状血管%肌细胞,平滑肌%二十二碳六烯酸类%大电导钙激活钾通道
冠狀血管%肌細胞,平滑肌%二十二碳六烯痠類%大電導鈣激活鉀通道
관상혈관%기세포,평활기%이십이탄륙희산류%대전도개격활갑통도
Coronary vessels%Myocytes,smooth muscle%Docosahexaenoic acids%Largeconductance calcium-activated potassium channels
目的 探讨二十二碳六烯酸(DHA)增加冠状动脉平滑肌细胞(SMC)大电导钙离子激活钾离子流(BK)的机制.方法酶消化法分离正常大鼠冠状动脉SMC.采用不同钾通道阻滞剂,对冠状动脉SMC的钾离子通道进行鉴定.采用全细胞膜片钳实验技术研究DHA及其代谢产物16,17-环氧二十二碳五烯酸(16,17-EDP)对冠状动脉平滑肌细胞BK通道的影响,并观察加入细胞色素P450环氧化酶抑制剂SKF525A孵育SMC后BK通道电流的变化.结果正常冠状动脉平滑肌细胞BK通道电流约占总钾离子流的(64.2±2.7)%(n=20).DHA可激活BK通道,半效浓度为(0.23±0.03)μmoL/L,但当使用细胞色素P450环氧化酶抑制剂SKF525A预孵育SMC后,DHA对BK通道的激活作用消失,而DHA代谢产物16,17-EDP可产生与DHA相同的BK通道激活作用,半效浓度为(19.7±2.8)nmol/L.结论 DHA通过细胞色素P450环氧化酶代谢途径激活平滑肌细胞BK通道,从而扩张冠状动脉.
目的 探討二十二碳六烯痠(DHA)增加冠狀動脈平滑肌細胞(SMC)大電導鈣離子激活鉀離子流(BK)的機製.方法酶消化法分離正常大鼠冠狀動脈SMC.採用不同鉀通道阻滯劑,對冠狀動脈SMC的鉀離子通道進行鑒定.採用全細胞膜片鉗實驗技術研究DHA及其代謝產物16,17-環氧二十二碳五烯痠(16,17-EDP)對冠狀動脈平滑肌細胞BK通道的影響,併觀察加入細胞色素P450環氧化酶抑製劑SKF525A孵育SMC後BK通道電流的變化.結果正常冠狀動脈平滑肌細胞BK通道電流約佔總鉀離子流的(64.2±2.7)%(n=20).DHA可激活BK通道,半效濃度為(0.23±0.03)μmoL/L,但噹使用細胞色素P450環氧化酶抑製劑SKF525A預孵育SMC後,DHA對BK通道的激活作用消失,而DHA代謝產物16,17-EDP可產生與DHA相同的BK通道激活作用,半效濃度為(19.7±2.8)nmol/L.結論 DHA通過細胞色素P450環氧化酶代謝途徑激活平滑肌細胞BK通道,從而擴張冠狀動脈.
목적 탐토이십이탄륙희산(DHA)증가관상동맥평활기세포(SMC)대전도개리자격활갑리자류(BK)적궤제.방법매소화법분리정상대서관상동맥SMC.채용불동갑통도조체제,대관상동맥SMC적갑리자통도진행감정.채용전세포막편겸실험기술연구DHA급기대사산물16,17-배양이십이탄오희산(16,17-EDP)대관상동맥평활기세포BK통도적영향,병관찰가입세포색소P450배양화매억제제SKF525A부육SMC후BK통도전류적변화.결과정상관상동맥평활기세포BK통도전류약점총갑리자류적(64.2±2.7)%(n=20).DHA가격활BK통도,반효농도위(0.23±0.03)μmoL/L,단당사용세포색소P450배양화매억제제SKF525A예부육SMC후,DHA대BK통도적격활작용소실,이DHA대사산물16,17-EDP가산생여DHA상동적BK통도격활작용,반효농도위(19.7±2.8)nmol/L.결론 DHA통과세포색소P450배양화매대사도경격활평활기세포BK통도,종이확장관상동맥.
Objective To investigate the mechanism of enhanced large conductance calciumactivated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA). Methods Coronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16,17-epoxydocosapentaenoic acid (16,17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration. Results BK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2±2.7)%of total potassium currents(n =20). DHA could activate BK channels, and its 50% effective concentration (EC50) was (0.23±0.03)μmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16,17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC50 was (19.7± 2.8) nmol/L.Conclusion DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.
