| Objective:To determine whether liver X receptor α(LXRα)can improve ventricular remodeling after myocardial infarction by inhibiting the NOX/ROS/TNF-α signal pathway;To study whether Naoxintong Capsule could improve ventricular remodeling and up-regulate LXRa mRNA expression;To study whether Naoxintong Capsule could inhibit NOX/ROS/TNF-α signaling pathway by regulating LXRa to improve ventricular remodeling.Methods:1.The rat model of acute myocardial infarction was established by coronary artery ligation Experiment 1:Rats were randomly divided into the sham operation group,model group,LXRa agonist group,and an LXRa inhibitor group,with 8 animals in each group.Experiment 2:Rats were randomly divided into the sham operation group,model group,statin group,low-dosegroup of Naoxintong,middle-dose group of Naoxintong,and high-dose group of Naoxintong,with 8 rats in each group.Experiment 3:Rats were randomly divided into the sham operation group,model group,Naoxintong group,and Naoxintong+LXRa inhibitor group,with 8 animals in each group.The sham operation group and the model group were administrated with 2ml/d saline,the LXRα agonist group was administered with LXRa agonist SR9238[30mg/(kg·d)],and the LXRa inhibitor group was administered with LXRa inhibitor GSK2033[30mg/(kg·d)],the statin group was given atorvastatin calcium tablets[5mg/(kg·d)],and the Naoxintong low,medium and high dose groups were administrated with concentrations of[0·19g/(kg·d)]、[0.38g/(kg·d)]、[0.76g/(kg·d)]Naoxintong capsule,the Naoxintong+LXRa inhibitor group was given the Naoxintong capsule at a concentration of 0.38g/kg+LXRa inhibitor GSK2033[30mg/(kg·d)]gavage for 4 weeks.2.Detection indicators:Left ventricular end diastolic diameter(LVIDd),left ventricular end systolic diameter(LVIDs),left ventricular ejection fraction(LVEF),and short-axis contraction rate(FS),Stroke volume(SV),cardiac output(CO)were checked by echocardiography.HE staining was used to observe the pathological changes of myocardial tissue.Masson staining was used to observe the degree of myocardial fibrosis;RT-QPCR was used to monitor expression of LXRα mRNA,reduced coenzyme Ⅱ oxidase(NOX)mRNA,reactive oxygen species(ROS),tumor necrosis factor-α(TNF-α)mRNA,and type Ⅰcollagen(COL Ⅰ)mRNA,type Ⅲ collagen(COL Ⅲ)mRNA in myocardial tissue.Result:1.Experiment 1:①Compared with the sham operation group,the echocardiography of the model group and the LXRa inhibitor group showed that LVIDd and LVIDs significantly increased(P<0.01),and EF,FS,SV,and CO significantly decreased(P<0.01).HE Staining showed a large number of myocardial cells disappeared,fibrous connective tissue hyperplasia and inflammatory cell infiltration.Masson staining showed collagen fibrosis,myocardial fibrosis.The expression of LXRa mRNA significantly reduced(P<0.01),expression of NOX mRNA,ROS,TNF-α mRNA,COL Ⅰ mRNA and COL Ⅲ mRNA significantly increased(P<0.01).②Compared with the model group and the LXRa inhibitor group,cardiac ultrasound in the LXRa agonist group showed significant decrease in LVIDd and LVIDs(P<0.01),a significant increase in EF,FS,SV,and CO(P<0.01).HE staining showed fibrous connectives tissues significantly reduced.Masson staining showed a significant decrease in collagen fibers.The expression of LXRa mRNA in cardiac tissue significantly increased(P<0.01),and the expression of NOX mRNA,ROS,TNF-α mRNA;COL ⅠmRNA,and COL Ⅲ mRNA significantly reduced(P<0.01).2.Experiment 2:①Compared with the sham operation group,cardiac ultrasound in the model group and the low-dose group of Naoxintong showed significant increase in LVIDd and LVIDs(P<0.01),and significant decrease in EF,FS,SV,and CO(P<0.01).HE staining showed a large number of myocardial cells disappeared,fibrous connective tissue hyperplasia and inflammatory cell infiltration.Masson staining showed collagen fibrosis,myocardial fibrosis.The expression of LXRa mRNA significantly reduced(P<0.01).The expression of NOX mRNA,ROS,TNF-α mRNA,COL Ⅰ mRNA and COL Ⅲ mRNA increased significantly(P<0.01).② Compared with the model group and low-dose group of Naoxintong,cardiac ultrasound in statin group,middle-dose,high-dose group of naoxintong group showed significant reductions in LVIDd and LVIDs(P<0.01),and significant decrease in EF,FS,SV,CO(P<0.01),HE staining showed a significant reduction in fibrous connective tissue.Masson staining showed a significant reduction in collagen fibers.The expression of LXRa mRNA significantly increased(P<0.01),expression of NOX mRNA,ROS,TNF-α mRNA,COL Ⅰ mRNA,COL Ⅲ mRNA significantly reduced(P<0.01).3.Experiment 3:①Compared with the sham operation group,cardiac ultrasound of the model group and the Naoxintong+LXRα inhibitor group showed that LVIDd and LVIDs significantly increased(P<0.01),and EF,FS,SV,and CO significantly decreased(P<0.01).HE Staining showed a large number of myocardial cells disappeared,fibrous connective tissue hyperplasia and inflammatory cell infiltration.Masson staining showed collagen fibrosis,myocardial fibrosis.The expression of LXRα mRNA significantly reduced(P<0.01).NOX mRNA,ROS,TNF-α mRNA,COL Ⅰ mRNA and COL Ⅲ mRNA significantly increased(P<0<01).②Compared with the model group and the Naoxintong+LXRαinhibitor group,cardiac ultrasound in the Naoxintong group showed significant reduction in LVIDd and LVIDs(P<0.01),significant increase in EF,FS,SV,and CO(P<0.01).HE staining showed fibrous connectives tissues significantly reduced.Masson staining showed a significant decrease in collagen fibers.The expression of LXRa mRNA in cardiac tissue significantly increased(P<0.01),and expression of NOX mRNA,ROS,TNF-α mRNA,COL Ⅰ mRNA,COL Ⅲ mRNA significantly reduced(P<0.01).Conclusion:1.LXRα could improve ventricular remodeling after myocardial infarction by inhibiting the NOX/ROS/TNF-α signaling pathway.2.Naoxintong Capsule could improve ventricular remodeling by inhibiting NOX/ROS/TNF-α signal pathway and up-regrating LXRα mRNA expression.3.Naoxintong Capsule could improve ventricular remodeling by up-regulating LXRα and inhibiting NOX/ROS/TNF-α signal pathway. |
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