Effects Of Dexmedetomidine On Myocardial Ischemic Injury And Its Relationship With RhoA/ROCK Signaling Pathway

Background: Coronary atherosclerotic heart disease(CHD)is a type of heart disease in which atherosclerotic lesions of the coronary arteries cause blockage or stenosis of the vascular cavity,leading to myocardial ischemia,hypoxia,and necrosis,acute myocardial infarction(AMI)is its most serious adverse consequence.At the time of myocardial infarction,a large number of apoptotic cells exist in the infarcted area and the non-infarcted area,which will seriously affect cardiac function.Therefore,inhibiting the apoptosis of myocardial cells after infarction is essential to cardiac function.Apoptosis is considered to be an important part of various physiological processes and is of great significance for maintaining the body’s homeostasis.In the process of normal growth and development,apoptosis is involved in maintaining the stability of the internal environment and maintaining the normal replacement of cells.In many human diseases,apoptosis can be seen and found as a form of programmed cell death.It has been confirmed that apoptosis can exert harmful effects in myocardial infarction and post-myocardial infarction complications in many ways.Therefore,it can protect against myocardial infarction by inhibiting some key pathways or key proteins in the process of apoptosis.As a selective α-2 receptor agonist,dexmedetomidine(DEX)has been used in clinical departments,for example,anesthesiology and ICU,and someday may use in other departments.Some studies on rats and mice prove that dexmedetomidine can protect multiple organs by reducing inflammation and reducing the activation of apoptotic pathways.Other studies have shown that dexmedetomidine has shown potential cardioprotective effects in both clinical and basic research.Therefore,we established a mouse myocardial infarction model to explore whether dexmedetomidine can protect the myocardium and explore its possible mechanism.Methods: The mouse model of myocardial infarction was established by ligating the anterior descending coronary artery.Five groups were divided: sham group(Sham),model group(MI),and three dexmedetomidine group(MI+DEX,5μg/kg/day,10μg/kg/day,20μg/kg/day).The mice in the sham group used a suture needle to pass through LAD without ligation.For the rest of the mice,the LAD was knotted with a prolene.After that,saline solution was injected into mice from the abdominal in the sham group and MI group.Dexmedetomidine working solution was injected into mice from the abdominal in three doses of dexmedetomidine daily for seven days.Blood was taken from puncturing of the retro-orbital vein plexus on the third day of intraperitoneal administration of mice,and the CK-MB content was measured after the serum was separated.On the seventh day of intraperitoneal administration,the mice were anesthetized with tribromoethanol and LVEF,LVFS and HR were measured by echocardiography.After blood was taken from the common cervical artery of the mouse,a centrifuge is used to prepare serum,and the specific content and specific activity of c Tn T,CK-MB and LDH in the serum are measured by Elisa and other methods.After the heart tissue is taken out,the blood in the heart is flushed and then fixed in 4%formaldehyde.After dehydration and embedding,HE,Sirius red,and immunohistochemical staining are made,and the data is analyzed by software.The rest of the heart tissue is used for Western blot experiments.By using chemiluminescence,the Cleaved Caspase-3,Cleaved Caspase-9,Bcl-2,Bax,ROCK1,and ROCK2 in the heart tissue can be observed under the imaging instrument,through the software view and analyze the results.Results: It was found through ultrasound that dexmedetomidine reduced the left ventricular dysfunction in mice with myocardial infarction and increased the LVEF and LVFS,while having a small effect on the heart rate.Serological examination found that dexmedetomidine reduce the levels of c Tn T,CK-MB and LDH in the serum of mice with myocardial infarction.HE and Sirius red staining showed that after using dexmedetomidine,the degree of myocardial injury and myocardial fibrosis can be significantly reduced.Western blot experiment results show that dexmedetomidine can reduce the expression of Cleaved Caspase-3,Cleaved Caspase-9,Bax,ROCK1,ROCK2 protein in the heart tissue of mice with myocardial infarction,and increase the anti-apoptotic protein Bcl-2 level.Conclusions: Dexmedetomidine protects the heart of mice with myocardial infarction by inhibiting cardiomyocyte apoptosis and improving cardiac function,and this cardioprotection may be related to the inhibition of Rho A/ROCK signaling pathway.