Diagnostic Ultrasonic Combined With Methyl Isoalizinin-1-methyl Ether To Improve Myocardial Microcirculation In Fiabetic Cardiomyopathy And Its Mechanism

Background Diabetic cardiomyopathy(DCM)is one of the main causes of heart failure and death in patients with diabetes.It refers to the abnormal structure and function of the heart due to the inherent myocardial dysfunction,which is not related to other vascular complications.DCM accounts for 50%-80% of deaths in patients with diabetes and is the leading cause of death in patients with type 2 diabetes.The pathogenesis of DCM is complex and may be related to calcium balance disorders,metabolic disorders,mitochondrial damage,and vascular dysfunction.There is no effective treatment for DCM clinically.Rubiadin-1-methyl ether(R1ME)is an anthraquinone compound isolated from Rubiaceae plants.It has general anthraquinone pharmacological effects such as anti-cancer,anti-inflammatory and improving myocardial fibrosis.Diagnostic-grade low-intensity ultrasound microbubble blasting technology(VFLASH)combined with R1 ME can effectively increase the local drug concentration and improve the therapeutic effect.As a new drug delivery technology,it provides a new way for targeted treatment of diabetic cardiomyopathy.Objective To investigate the effect and mechanism of VFLASH combined with R1 ME in improving cardiac microcirculation by observing the effect of cardiac function in the DCM rats.Methods 1.The DCM rat model was established by intraperitoneal injection of streptozotocin and feeding on a high-sugar and high-fat diet for 4 weeks.The cardiac function of rats wasmeasured by animal echocardiography.2.MDA content detection kit and SOD activity detection kit were used to detect MDA content and SOD activity in serum.3.Myocardial tissue morphology of DCM rats was detected by HE staining,Masson staining and VG staining.4.The NO content detection kit was used to detect the release amount of NO.5.Western blot was used to detect the expression of PI3 K,Akt and e NOS in myocardial tissue of DCM rats.6.Immunohistochemical detection of PI3 K,Akt and e NOS expression in DCM rat myocardial tissue.7.Immunohistochemistry was used to detect the expression of neovascularization marker CD31 in rat cardiac muscle.Results 1.The heart function of the rats was measured using an animal cardiac ultrasound system.The heart function of the rats in the Model group was weakened,and the heart function of the rats in the VFLASH + R1 ME group was improved.2.The content of MDA in serum and the activity of SOD were decreased in Model group.The content of MDA in VFLASH+R1ME group increased,and the activity of SOD increased.3.HE staining and Masson staining and VG staining results show that the Model of myocardial fibers arranged disorder without compliance,muscle fiber structure fuzzy,wider intercellular space,myocardial cell morphology change obviously,cell hypertrophy of swelling,deformation,the nucleus volume increased obviously,and myocardial cells between the presence of large amounts of fibroblast and inflammatory cells infiltration.The myocardial morphology of rats in VFLASH + R1 ME group tended to be normal.4.The NO content in the serum of the Model group decreased,and the NO content in the serum of the VFLASH + R1 ME group increased.5.The results of Western blots showed that the expression of PI3 K,Akt and e NOS in the myocardial tissue of the Model group was reduced,while the expression of PI3 K,Akt and e NOS in the myocardial tissue of the VFLASH + R1 ME group was increased.6.The results of immunohistochemistry showed that the expression levels of PI3 K,Akt and e NOS in the myocardial tissue of the Model group were reduced,while the expression levels of PI3 K,Akt and e NOS in the myocardial tissue of the VFLASH + R1 ME group were increased.7.The results of immunohistochemistry showed no significant change in the expression of the neovascular marker CD31 in the myocardial tissue of the Model group,and the expression of the neovascular marker CD31 in the VFLASH + R1 ME group increased.