摘要
目的观察补肾活血组方对心肌梗死(心梗)后心力衰竭大鼠心肌组织β-连锁蛋白(β-catenin)、散乱蛋白1(Dishevelled1,Dvl1)及轴抑制蛋白2(Axin2)、细胞周期蛋白D1(Cyclin D1)、电压门控钾通道蛋白4.3(voltagegated K+channel4.3,KV4.3)mRNA的影响。方法将13周龄雄性60只SD大鼠随机分为空白组15只和实验组45只。实验组大鼠通过结扎冠脉左前降支联合力竭式游泳、饥饿,建立心梗后心衰模型。造模成功的大鼠随机分3组,即模型组、赖诺普利组及补肾活血组。赖诺普利组灌胃赖诺普利混悬液1.5 mg/kg,补肾活血组灌胃补肾活血方熬制汤剂9.2 mg/kg,空白组和模型组灌胃等体积蒸馏水,各组均2次/d。灌胃4周后,心脏超声检测左室收缩末内径(left ventricular end systolic diameter,LVESD)、左室舒张末内径(left ventricular end diastolic diameter,LVEDD)、射血分数(ejection fraction,EF)及左室短轴缩短分数(shortening fraction,FS),酶联免疫吸附法测定血清N末端B型利钠肽前体(N-terminal pro brain natriuretic peptide,NT-proBNP)、Wnt3a、Wnt5a、Wnt11、Dickkopf-1(DKK1)、分泌性FZD相关蛋白1(secreted Frizzled-related proteins,sFRP1)、Wnt抑制蛋白1(Wnt inhibitory protein,WIF1)含量,免疫组化法检测大鼠心肌β-catenin、Dvl1表达,反转录聚合酶链式反应法检测Axin2、Cyclin D1、KV4.3 mRNA表达。结果与空白组比较,模型组大鼠LVEDD、LVESD升高,EF、FS降低,血清NT-proBNP、DKK1、sFRP1、WIF1含量和心肌组织β-catenin、Dvl1蛋白及Cyclin D1、KV4.3mRNA表达升高(P<0.05),血清Wnt3a、Wnt5a、Wnt11及心肌组织Axin2mRNA表达降低(P<0.05)。与模型组比较,赖诺普利组和补肾活血组大鼠LVEDD、LVESD降低,EF、FS升高,血清NT-proBNP、DKK1、sFRP1、WIF1含量和心肌组织β-catenin、Dvl1蛋白及Cyclin D1、KV4.3mRNA表达降低(P<0.05),血清Wnt3a、Wnt5a、Wnt11及心肌组织Axin2mRNA表达升高(P<0.05)。结论补肾活血组方可能通过下调心梗后心衰大鼠β-catenin、Dvl1蛋白和Cyclin D1、KV4.3mRNA及DKK1、sFRP1、WIF1表达,上调Axin2mRNA及Wnt3a、Wnt5a、Wnt11表达,改善心功能,延缓心室重构,防止心衰发展。
Objective To observe the effect of kidney-tonifying and blood-activating herbs onβ-Catenin and Dishevelled1(Dvl1)as well as Axin2,Cyclin D1 and KV4.3 mRNA in myocardial tissue of rats with heart failure after myocardial infarction.Methods Sixty male 13-week old SD rats were randomly divided into 15 rats in the blank group and 45 rats in the experimental group.The rats in the experimental group established the model of heart failure after myocardial infarction by ligating the left an⁃terior descending coronary artery combined with exhaustive swimming and starvation.The successful rats were randomly divided into three groups:model group,lisinopril group and kidney-tonifying and blood-activating group.The lisinopril group was given lisinopril suspension with the dose of 1.5 mg/kg by gavage,the kidney-tonifying and blood-activating group was treated with kidney-tonifying and blood-activating formula with the dose of 9.2 g/kg,and the blank group and model group were given the distilled water with the equal volume,twice a day in each group.After 4 weeks of gavage,left ventricular end systolic diameter(LVESD),left ventricular end diastolic diameter(LVEDD),ejection fraction(EF)and left ventricular short axis shortening frac⁃tion(FS)were measured by echocardiography,the contents of serum N-terminal pro brain natriuretic peptide(NT-proBNP),Wnt3a,Wnt5a,Wnt11,Dickkopf-1(DKK1),secreted frizzled-related proteins(SFRP1)and Wnt inhibitory protein(WIF1)were measured by enzyme-linked immunosorbent assay,andβ-Catenin and DVL1 of the myocardium of rats were detected by immunohistochemistry and Axin2,cyclin D1 and KV4.3 mRNA expressions were detected by real-time quantitative polymerase chain reaction.Results Compared with those of the blank group,LVEDD and LVESD increased,EF and FS decreased,the con⁃tents of NT-proBNP,DKK1,SFRP1 and WIF1 in serum and the expressions ofβ-Catenin and Dvl1 as well as Cyclin D1 and KV4.3 mRNA in myocardial tissue increased(P<0.05),and the expressions of Wnt3a,Wnt5a and Wnt11 in serum and Axin2 mRNA in myocardial tissue decreased in the model group(P<0.05).Compared with those of the model group,LVEDD and LVESD decreased,EF and FS increased,the contents of NT-proBNP,DKK1,SFRP1 and WIF1 in serum and the expressions ofβ-Catenin and Dvl1 as well as Cyclin D1 and KV4.3 mRNA in myocardial tissue decreased(P<0.05),and the expressions of Wnt3a,Wnt5a and Wnt11 in serum and Axin2 mRNA in myocardial tissue increased(P<0.05)in lisinopril group and kidney-tonifying and blood-activating group.Conclusion Kidney-tonifying and blood-activating formula may down-regulate the ex⁃pressions ofβ-Catenin and Dvl1,Cyclin D1 and KV4.3 mRNA,DKK1,SFRP1 and WIF1 in heart failure rats after myocardial infarction,up-regulate the expressions of Axin2 mRNA,Wnt3a,Wnt5a and Wnt11,improve the cardiac function,delay the ven⁃tricular remodeling and prevent the development of heart failure.
作者
许瑞
张艳
何佳
孔繁达
尹举
张伟
尹文浩
邹文聪
XU Rui;ZHANG Yan;HE Jia;KONG Fanda;YIN Ju;ZHANG Wei;YIN Wenhao;ZOU Wenchong(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China;Post-Doctoral Mobile Station of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The First Affiliated Hospital of Shanxi University of Traditional Chinese Medicine,Taiyuan 030024,Shanxi,China)
出处
《中华中医药学刊》
CAS
北大核心
2023年第2期132-136,I0021,I0022,共7页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81774157,82174241)。
