乌头碱中毒及双黄连干预对心肌雷诺定受体表达的影响

Effects of aconitine poisoning and Shuang-huang-lian treatment on the expression of myocardial ryanodine receptor

目的:研究乌头碱中毒及双黄连注射液干预对心肌雷诺定受体(rynanodine receptor 2,Ry R2)表达的影响,探讨双黄连对抗乌头碱致心律失常毒性的作用机制。方法:将52只SD大鼠随机分成3组:乌头碱组(A组,n=20),双黄连组(B组,n=20)和对照组(C组,n=12)。A,B两组先予乌头碱0.3 mg/kg灌胃,30 min后A组予生理盐水腹腔注射,B组予双黄连100 mg/kg腹腔注射;对照组两次均予生理盐水处理,连续给药10 d。于第1,3,6,10天记录大鼠心电图变化并进行心律失常评分,采用免疫荧光染色及实时定量PCR技术检测大鼠心肌组织Ry R2蛋白及基因的表达变化。结果:各时间点B组的心律失常评分均较A组低,差异有统计学意义(P<0.05或P<0.01);第1天A组心肌Ry R2蛋白及Ry R2m RNA表达即较B,C两组增加,但差异无统计学意义(P>0.05);第3,6,10天A组Ry R2蛋白及Ry R2 m RNA表达较B,C两组均显著增加,差异有统计学意义(P<0.01)。结论:双黄连可有效治疗乌头碱中毒引起的心律失常,其机制可能与降低乌头碱引起的Ry R2异常高表达有关。

Objective： To study the impact of aconitine and Shuang-huang-lian injection on the expression of myocardial ryanodine receptor（Ry R2） and to discuss the anti-arrhythmic mechanisms of Shuanghuanglian against aconitine poisoning.Methods： A total of 52 SD rats were randomly divided into 3 groups： aconitine group（group A, n=20）, Shuang-huang-lian group（group B, n=20） and control group（group C, n=12）. Aconitine at a dose of 0.3 mg/kg was fi rstly administrated to the rats of group A and group B through gavage. 30 minutes later, normal saline was delivered to rats in group A through intraperitoneal injection,while rats in group B received Shuang-huang-lian at a dose of 100 mg/kg through intraperitoneal injection. Group C accepted twice administration of normal saline by gavage and intraperitoneal injection. The disposals for each group were implemented for 10 consecutive days. The rats＇ electrocardiograms（ECG） were recorded on day 1, 3, 6 and 10. Immunofluorescent staining technique and real-time quantitative PCR technique was used to detect the protein and m RNA expression of myocardial RyR 2.Results： The arrhythmia scores of group B at different time were lower than group A and the difference was statistically significant（P〈0.05 or P〈0.01）. The protein and m RNA expression of RyR 2 in group A was slightly increased on the first day compared to group B and group C, with no statistical significance（P〈0.05）. On day 3, 6 and 10, the expression of RyR 2 protein and m RNA in group A was dramatically increased compared to group B and group C（P〈0.01）. Conclusion： Shuang-huang-lian injection can effectively prevent the arrhythmia caused by aconitine, which is related to suppressing the aconitine-induced RyR 2 expression.