| Background and ObjectiveHeart Failure(HF)has become one of the most important public health problems in the world.At present,the treatment strategy of left heart failure has developed from the traditional "golden triangle"(β-blocker,ACEI/ARB and halocorticoid receptor antagonist)to the "new quadruple" with SGLT2 inhibitor.With the continuous optimization of the treatment of left heart failure,the prevention and treatment of right heart failure has gradually entered the field of medical vision.At present,the treatment of right heart failure is mainly to reduce afterload,control preload,enhance myocardial contractility,etc.However,the clinical effect is not ideal,many drugs to improve left ventricular remodeling do not have the same effect on right heart failure.Therapeutic targets and drugs for right heart failure need to be studied.Sodium-glucose cotransporter 2(SGLT2)inhibitors are effective antidiabetic agents in patients with type 2 diabetes.Their main effects are to block glucose reabsorption in the proximal curving tubules of the kidney and increase urine glucose to improve blood glucose control.Surprisingly,in a large cardiovascular outcome trial(name it)in diabetic patients,SGLT2 inhibitors improved cardiovascular outcome,reversed partial left heart remodeling,and reduced left ventricular heart failure hospitalizations,a benefit also seen in patients with reduced ejection fraction heart failure.However,the therapeutic effect and potential mechanism of SGLT2 inhibitors on right cardiac remodeling remain unclear.Through animal experiments,we found that SGLT2 inhibitors can improve right ventricular remodeling.Combined with bioinformatics analysis of left and right ventricular differential genes in the database,we proposed a hypothesis that SGLT2 inhibitors participate in the improvement of right ventricular remodeling by regulating left and right ventricular differential genes.In order to explore the therapeutic effects of left and right ventricular differential genes and SGLT2 inhibitors on right heart remodeling,the following experiments were designed.Method1.Establishment of right ventricular myocardial infarction(RVI)modelMale C57BL/6 mice(8 weeks of age)were randomly divided into RVI group and sham operation group.The mice were anesthetized by intraperitoneal injection and connected with ventilators after endotracheal intubation.The right coronary artery branch was ligated 3-5mm from the beginning of the right ventricle with 8-0 nylon suture,and ST-segment elevation confirmed myocardial ischemia on ECG.2.Echocardiography and right heart catheterizationEchocardiography of mice was observed every week after surgery until 28 days.Right ventricular function was assessed by ultrasound.Right ventricular function was repeatedly verified by right cardiac pressure catheter test before sampling.3.Histological stainingThe mouse heart tissue was fixed,flushed,dehydrated and embedded to prepare paraffin samples.The tissue with a thickness of 3μm was cut into sections by the slicer.After dewaxing,Masson staining was performed and the infarct area was analyzed by photographing.Result1.Successful establishment of right myocardial infarction modelLead Ⅲ ST segment elevation in mice during operation,TTC staining of the heart one day after operation showed right ventricular infarction.One week after surgery,the short axis of the right ventricle was enlarged and the function of the right ventricle was impaired.2.Differential gene analysis of left and right ventriclesMitotic pathway genes were up-regulated in the hypoxic right heart compared with hypoxic left heart,and genes related to hypertrophy such as oxygen transport were down-regulated.3.Dagaglizin relieves right ventricular remodelingTTC staining of Dapagliflozin(Dapa)treated mice one day after RVI showed a decrease in infarct area of right ventricle,and Tunel staining showed a decrease in apoptotic cells of Dapa treated mice.28 days after Dapa treatment,cardiac ultrasound and right heart catheterization showed that the function of the ultra-right ventricle was improved in the treatment group,and histological staining showed that the right ventricle fibrosis decreased and viable myocardium increased in the treatment group.ConclusionThe model of right myocardial infarction was established successfully,and daglizhin improved right ventricular remodeling. |
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