芪参益气滴丸干预心肌梗死大鼠免疫与炎性反应的机制

Protection of Qishen Yiqi Pills on Rats with Myocardial Infarction of Qi deficiency and blood stasis

目的观察芪参益气滴丸的心肌保护作用及对糖原合成激酶-3β(GSK-3β)通路影响的机制。方法雄性SD大鼠46只,随机分为正常组、模型对照组、实验模型组、硝酸异山梨醇酯组、芪参益气组。建立心肌梗死模型和气虚血瘀证心肌梗死模型,分别用硝酸异山梨醇酯和芪参益气滴丸干预,观察心脏射血分数(EF)、心肌梗死情况和心肌组织的TRL4、NF-κB、GSK-3β、β-catenin的蛋白和基因表达。结果取材后心肌组织NBT染色后,正常组心肌组织显示紫黑色;各模型组的心肌组织可见有大片的灰白色梗死区域,各给药组的心肌组织可见有较小的灰白色梗死区。各模型组EF明显低于正常组,硝酸异山梨醇酯组、芪参益气组均能改善心功能,差异有显著性(P<0.01)。免疫组化结果示,正常组GSK-3β和TRL4蛋白阳性表达细胞百分比较低,各模型组均高于正常组(P<0.01);硝酸异山梨醇酯和芪参益气滴丸能够降心肌组织的GSK-3β和TRL4蛋白阳性表达(P<0.01)。RT-PCR结果显示,正常组β-catenin基因相对表达量最高,NF-κB基因相对表达量最低,各模型组β-catenin基因表达低于正常组,NF-κB基因表达高于正常组(P<0.01);硝酸异山梨醇酯和芪参益气滴丸能够促进β-catenin基因表达抑制NF-κB基因表达(P<0.01)。结论芪参益气滴丸的心肌保护作用可能通过调节TRL4/NF-κB、GSK-3β/β-catenin通路来抑制心肌细胞凋亡实现的。

Objective To observe the protection and its mechanism of Qishen Yiqi dripping pills on myocardial.Methods 46 male SD rats were randomly divided into normal group,model control group,experimental model group,isosorbide dinitrate(ISD) group,Qishen Yiqi(QSYQ) group.Establishment of myocardial infarction models and the deficiency of Qi and blood stasis myocardial infarction model,respectively,with isosorbide dinitrate and Qishen Yiqi Drop Pill intervention.Cardiac ejection fraction,myocardial infarction and myocardial tissue GSK-3β,TRL4,NF-κB,β-catenin protein and gene expression were observated.Results After NBT staining,myocardial tissue in the normal group were stained purple;There were large grey infarcted region in myocardial tissue 0f each model group.There were smaller gray infarction area than ISD group and QSYQ group.The model group,ejection fraction(EF) signi?cantly lower than the normal group;Qishen Yiqi group could improve cardiac function(P<0.01).Immunohistochemical results shown,the normal group GSK-3β and of TRL4 protein expression was low,the model group were higher than those in normal group(P<0.01);isosorbide dinitrate and Qishen Yiqi Drop Pill could increase GSK-3β and TRL4 protein expression(P<0.01).RT-PCR results show,β-catenin gene expression level was sthe highest and NF-κB gene level was lowest in the normal group,the model group β-catenin gene level was lower than that in normal group and NF-κB gene level was higher than that in normal group(P<0.01);Qishen Yiqi Drop Pill could increase β-catenin gene expression and decrease NF-κB gene level(P<0.01).Conclusion The effect of Qishen Yiqi Drop Pill on myocardial protection may be relate to regulation of TRL4/NF-κB,GSK-3β/β-Catenin pathway.