红景天苷对大鼠缺血再灌注心律失常及心肌Cx43的影响  

Effect of salidroside on ischemia-reperfusion arrhythmia and myocardium celluar Cx43 protein

作　　者：何阳 李福森[1] 陆俊鸿 黄晓亮[1] 李映新[1] HE Yang;LI Fusen;LU Junhong;HUANG Xiaoliang;LI Yingxin(College of Pharmacy,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《沈阳药科大学学报》2025年第4期381-387,394,共8页Journal of Shenyang Pharmaceutical University

基　　金：广西自然科学基金青年基金项目(2017GXNSFBA198151)。

摘　　要：目的研究红景天苷(salidroside,Sal)预处理后对再灌注心律失常(reperfusion arrhythmia,RA)及心肌连接蛋白43(connexin 43,Cx43)的影响。方法取心电图正常的50只SPF级SD大鼠随机分为假手术组(Sham组),模型组(I/R组),Sal低、高剂量组(12、36 mg·kg^(-1))和联合抑制剂组[Sal(36 mg·kg^(-1))+LY294002(0.3 mg·kg^(-1))]。建立心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)模型,手术全程观测Ⅱ导联心电图并对再灌注心律失常严重性评分,术后行TTC染色,检测血清肌酸激酶同工酶(creatine kinase-MB,CK-MB)、肌钙蛋白I(cardiac troponin I,cTnI)和肿瘤坏死因子-α(tumor necrosis factor,TNF-α)含量;免疫组织化学法观察Cx43在心肌组织的分布和表达;蛋白质印迹法(Western-blotting)分别检测PI3K、Akt、Cx43的蛋白表达及其磷酸化水平。结果与I/R组和PI3K抑制剂组相比,Sal高剂量组的室性早搏(premature ventricular contraction,PVC)的次数和室性心动过速(ventricular tachycardia,VT)总持续时间均减少,心律失常评分指标有所改善(P均小于0.05或0.01),但心室颤动(ventricular fibrillation,VF)次数无明显差异(P>0.05),CK-MB、cTnI和TNF-α含量减少(P均小于0.05或0.01),心肌梗死面积百分比下降(P<0.05),Cx43在心肌组织侧面分布减少,端-端分布增加,平均光密度值(average optical density,AOD)增加(P<0.05),上调Cx43、p-Cx43、p-PI3K、p-Akt的蛋白水平,增加p-Cx43/Cx43、p-PI3K/PI3K和p-Akt/Akt比值(P均小于0.05或0.01)。结论红景天苷可能通过激活PI3K/Akt通路调控心肌Cx43减少再灌注心律失常的发生频率及恶性程度。Objective To study the effect of salidroside(Sal)on reperfusion arrhythmia(RA)and myocardial connexin 43(Cx43)regulation.Methods SD rats(n=50)with normal ECG were randomly divided into Sham group,ischemia-reperfusion group(I/R group),Sal low dose group(12 mg·kg~(-1)),Sal high dose group(36 mg·kg~(-1))and combined inhibitor group:Sal(36 mg·kg~(-1))+LY294002(0.3 mg·kg~(-1)).Except for Sham group.The models of myocardial ischemia-reperfusion injury were established and ECG during the whole experiment period were recorded to score the severity of the reperfusion arrhythmia.The area of myocardial infarction was measured by TTC staining,Serum creatine kinase isozyme(CK-MB),cardiac troponin I(cTnI),and tumor necrosis factor-α(TNF-α)content were determined.The distribution and expression of Cx43 in myocardial tissue were detected by immunohistochemical method.The protein expression and phosphorylation of PI3K,Akt and Cx43 were detected by Western-blotting.Results Although there was no significant difference in ventricular fibrillation(VF)(P>0.05),the number of premature ventricular contraction(PVC),the duration of ventricular tachycardia(VT)and the arrhythmia score of Sal high-dose group were significantly decreased compared with the I/R and combined inhibitor groups(P<0.05 or 0.01).The area of myocardial infarction was lower and the content of CK-MB,cTnI,and TNF-α were decreased(P<0.05 or 0.01),the distribution of Cx43 was relatively regular and the average optical density value(AOD)was significantly increased.The expression of Cx43,p-Cx43,p-PI3K,and p-Akt were up-regulated and p-Cx43/Cx43,pPI3K/PI3K,and pAkt/Akt ratios of protein were also increased(P<0.05 or 0.01)in Sal high-dose group.Conclusion Salidroside inhibits ischemia-reperfusion arrhythmia and the mechanism maybe associated with regulating myocardial Cx43 by activating the PI3K/Akt pathway.

关 键 词：红景天苷 PI3K AKT CX43 心肌缺血再灌注 心律失常 

分 类 号：R96[医药卫生—药理学]