CAJ | 학술논문

目的：观察异长春花苷内酰胺大剂量注射给药对麻醉Beagle犬心血管系统的影响，并考察其体外对离子通道的抑制作用。方法：采用生理记录仪观察异长春花苷内酰胺静脉注射前后不同时间点Beagle犬收缩压（Sys），舒张压（Dia），平均动脉压（MBP），心率（HR），心电图PR间期、QRS间期、QT间期、QTcb间期、QTcv间期等指标的变化；应用全细胞膜片钳技术考察不同浓度异长春花苷内酰胺对CHO-hERG细胞上hERG钾离子通道和HEK-293-Nav1.5细胞上Nav1.5钠离子通道的抑制作用。结果：与空白对照组相比，异长春花苷内酰胺60、18 mg·kg-1剂量组、溶媒对照组（含吐温-80）于给药后15 min Sys、Dia、MBP、HR明显降低（P<0.05），给药结束后各项指标可见恢复。与溶媒对照组相比，各给药剂量组在各观测时间点无显著性差异。与空白对照组及自身给药前相比，60、18、6 mg·kg-1剂量组、溶媒对照组于给药后15 min QT、QTcb、QTcv间期明显延长（P<0.05），给药结束后可见一定程度的恢复。与溶媒对照组相比，各给药剂量组QT、QTcb和QTcv间期在各观测时间点无显著性差异。异长春花苷内酰胺对hERG钾离子通道和Nav1.5离子通道抑制作用较弱，IC50为560.8μmol·L-1及>900μmol·L-1，远远大于阳性对照药。结论：异长春花苷内酰胺大剂量单次静脉注射对Beagle犬可能有一定的降低血压、减慢心率及延长QT间期的作用，停药后可恢复。其中血压降低、心率减慢与溶媒中所含吐温-80有关。体外对hERG钾离子通道和Nav1.5离子通道无明显影响，提示异长春花苷内酰胺对动物QT间期的影响可能为其它作用机制所致。
목적：관찰이장춘화감내선알대제량주사급약대마취Beagle견심혈관계통적영향，병고찰기체외대리자통도적억제작용。방법：채용생리기록의관찰이장춘화감내선알정맥주사전후불동시간점Beagle견수축압（Sys），서장압（Dia），평균동맥압（MBP），심솔（HR），심전도PR간기、QRS간기、QT간기、QTcb간기、QTcv간기등지표적변화；응용전세포막편겸기술고찰불동농도이장춘화감내선알대CHO-hERG세포상hERG갑리자통도화HEK-293-Nav1.5세포상Nav1.5납리자통도적억제작용。결과：여공백대조조상비，이장춘화감내선알60、18 mg·kg-1제량조、용매대조조（함토온-80）우급약후15 min Sys、Dia、MBP、HR명현강저（P<0.05），급약결속후각항지표가견회복。여용매대조조상비，각급약제량조재각관측시간점무현저성차이。여공백대조조급자신급약전상비，60、18、6 mg·kg-1제량조、용매대조조우급약후15 min QT、QTcb、QTcv간기명현연장（P<0.05），급약결속후가견일정정도적회복。여용매대조조상비，각급약제량조QT、QTcb화QTcv간기재각관측시간점무현저성차이。이장춘화감내선알대hERG갑리자통도화Nav1.5리자통도억제작용교약，IC50위560.8μmol·L-1급>900μmol·L-1，원원대우양성대조약。결론：이장춘화감내선알대제량단차정맥주사대Beagle견가능유일정적강저혈압、감만심솔급연장QT간기적작용，정약후가회복。기중혈압강저、심솔감만여용매중소함토온-80유관。체외대hERG갑리자통도화Nav1.5리자통도무명현영향，제시이장춘화감내선알대동물QT간기적영향가능위기타작용궤제소치。
This study was aimed to investigate the effects of high-dose strictosamide injection on cardiovascular sys-tem of anesthetized beagle dogs and to examine the inhibition of strictosamide on ion channels in vitro. Indexes such as changes of systolic blood pressure (Sys), diastolic blood pressure (Dia), mean blood pressure (MBP), heart rate (HR), PR, QRS, QT, QTcb and QTcv at different time points before and after strictosamide injection in dogs were monitored by the polygraph system. The inhibition of strictosamide at different concentrations on hERG potassium channel in CHO-hERG cells and Nav1.5 sodium channel in HEK-293-Nav1.5 cells were measured by whole-cell patch-clamp method. The results showed that compared with the blank control group, Sys, Dia, MBP and HR were obviously declined 15 min after medication in the strictosamide (60, 18 mg·kg-1) group and the vehicle-control group (containing tween-80) (P < 0.05). After medication, all indexes were recovered. Compared to the vehicle-control group, there were no significant differences at different time points in each medication groups. Compared with the blank control group and before medication, the QT interval, QTcb and QTcv were significantly prolonged 15 min af-ter medication in the strictosamide (60, 18, 6 mg·kg-1) group and the vehicle-control group (P< 0.05). When medi-cation stopped, indexes were recovered at certain level. Compared with the vehicle-control group, there were no sig-nificant differences of QT interval, QTcb and QTcv of each medication group at different time points (P> 0.05). The inhibition of strictosamide on hERG potassium channel and Nav1.5 sodium channel were weak with IC50 values of 560.8 μM and > 900 μM, respectively, which were far greater than the positive controls. It was concluded that sin-gle, high-dose intravenous injection of strictosamide may lead to a lower blood pressure, a slower heart rate and a prolongation on the QT interval in beagle dogs, which returned to basal levels when medication stopped. It was spec-ulated that the reduction of blood pressure and the slowing of heart rate were related to tween-80 contained in the vehicle control group. No significant inhibitory effects were detected on hERG potassium channel and Nav1.5 sodium channel in vitro, which suggested that other mechanisms may be involved in strictosamide-induced QT interval pro-longation in animals.