右美托咪定对布比卡因致心脏毒性的影响

The effect of dexmedetomidine on bupivacaine induced cardiotoxicity

目的探讨右美托咪定(Dexmedetomidine)对布比卡因所致心脏毒性的影响。方法培养人冠状动脉内皮细胞,分为对照组(细胞不做任何处理);右美托咪定组(200μg/L右美托咪定作用2h);布比卡因组(1000μM布比卡因作用2h);右美托咪定+布比卡因组(右美托咪定和布比卡因作用2h);右美托咪定+布比卡因+PI3K抑制剂组[右美托咪定、PI3K抑制剂LY294002(20μM)及布比卡因作用2h]。造模结束后,收集细胞及培养基。Transwel检测细胞对布比卡因的通透性。采用细胞计数试剂盒(CCK-8)检测细胞活性;蛋白质印迹法(WB)检测Z01、PI3K、p-Akt/Akt.p-PTEN/PTEN等蛋白。结果右美托咪定降低内皮细胞对布比卡因的通透性(P=0.002),增加ZO-1蛋白的表达量(P<0.001),但加入PI3K抑制剂后上述作用消失。右美托咪定增加PI3K及Akt蛋白的表达(P<0.001)。结论右美托咪定通过PI3K/Aki通路调节ZO-1蛋白降低心脏血管通透性,最终增强心脏对布比卡因毒性的耐受性。

Objective To study the efects and causes of dexmedetomidine on cardiotoxicity caused by bupivacaine.Methods Human coronary endothelial cells were cultured and grouped as follows:1.Control group con:the cells were not treated;2.Dexmedetomidine roup dex:200μg/L dexmedetomidine fixed action for 2hours;3.Bupivacaine group(Bupivacaine Bupi):1000μM bupivacaine for 2hours;4.dexmedetomidine+bupivacaine group(DB):dexmedetomidine and bupivacaine Caine for 2hours.5.Dexmedetomidine+bupivacaine+PI3K inhibitor group(DB-inhibitor):Dexmedetomidine,PI3K inhibitor LY294002(20μM)and bupivacaine for 2hours.Afer the modeling,the cells and culture medium were ollcted.Transwell measures the permeability of cell to bupivacaine.Cell counting activity(Cell Counting Kit-8,CCK-8)was used to detect cell viability;Western blot(WB)was used to detect Z01,PI3K,p-Akt/Akt,p-PTEN 1 PTEN and other proteins.Results Dexmedetomidine decreased the permeability of endothelial cells to bupivacaine(Bupi vs DB P=0.002)and increased the expresion of ZO-1 protein(DB vs Bupi P<0.001),but in After adding PI3K inhibitor,the above ffct disappeared.Dexmedetomidine increased the expression of PI3K and Akt protein(P<0.001).Conclusion Dexmedetomidine regulates the ZO-I protein through the PI3K 1 Akt pathway to reduce cardiac vascular permeability and ultimately enhance the heart's tolerance to bupivacaine toxicity.