| Objective: The heart is one of the most important organs of the human body and provides power for the life activities of the human body.In today’s society,the high incidence of cardiomyopathy and myocardial-related diseases has a serious impact on human health and has greatly increased the social and economic burden.In addition,in the past few decades,the incidence of overweight and obesity has increased at an extremely rapid rate.Obesity can lead to the occurrence and development of heart disease,obesity-related cardiomyopathy,and diabetic cardiomyopathy,and cause myocardial dysfunction.The transcription factor Nfe2l1(Nuclear factor erythroid-2-related factor 1),as a key factor that regulates cellular adaptive antioxidant response and proteasome homeostasis,participates in a variety of important regulatory roles in the body.This thesis is divided into two parts.The first part is to explore the effect of Nfe2l1 gene deletion on myocardial function from the perspective of genetic factors;the second part is to explore the impact of obesity on myocardial function from the perspective of environmental factors.From these two perspectives,it provides a new experimental theoretical basis for finding ways to prevent and treat myocardial diseases characterized by myocardial dysfunction.Methods:1.Use the Cre-Lox P recombinase system and breeding strategy to construct a Nfe2l1 knockout mouse model of cardiomyocytes;2.Use scales,blood glucose meters,clinical thermometers,body composition meters and metabolic cages to monitor the basal metabolism-related indicators of mice;3.Use animal blood pressure meter to detect blood pressure and pulse of mice;4.Use echocardiography to detect myocardial function in mice;5.Use HE staining of histopathological sections to observe the general state of mouse myocardial tissue;6.Use RT-qPCR technology to detect the expression level of mouse NFE2L1 and the expression level of antioxidant-related indicators;7.Use Western blot to detect the expression level of mouse NFE2L1 and the protein expression level of antioxidant-related indicators.Results:1.Through the genotype identification results and RT-qPCR detection of m RNA levels,it can be seen that the myocardial cell Nfe2l1 knockout mouse model was successfully established;after the relevant index function test,compared with the control group,the basis weight of the cardiomyocyte Nfe2l1 knockout mouse,Body temperature,blood sugar,blood pressure and pulse,echocardiographic parameters and the gross structure of HE stained myocardial tissues were not significantly different.2.After 3 months of feeding,compared with mice on a normal diet,mice on a high-fat diet gained weight,increased blood sugar,and significantly increased body fat;compared with mice on a normal diet,the high-fat diet was smaller Rats have a faster pulse,no obvious changes in blood pressure,lower ejection fraction and short-axis shortening rate detected by echocardiography,increased left ventricular myocardium mass,ventricular septal thickness,heart weight,and HE staining myocardial fiber disorder;detection of related m RNA Compared with the control group,the expression level of NFE2L1 in myocardial tissue of obese mice induced by high-fat diet increased,and the protein expression of glutamylcysteine ligase catalytic subunit and heme oxygenase 1 increased.Conclusion:1.Under the premise of the experimental methods currently used in this study,the deletion of the Nfe2l1 gene in mouse cardiomyocytes has no significant effect on myocardial function.2.Mice fed with a high-fat diet for 3 months became obese.Obese mice induced by high-fat diet decreased myocardial contractility and myocardial dysfunction.Obese mice induced by high-fat diet increased the expression level of NFE2L1 in myocardial tissue.The antioxidant level is increased. |
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