动物造模,心力衰竭模型,药效评价 zi-bio 2024-10-23 1056

　　Adult mice exhibit hemodynamic and clinical signs similar to human HF. Therefore, using gene knockout or transgenic mouse models to alter the expression of heart specific genes, and studying the roles and mechanisms of certain genes in cardiac development, development, and HF are valuable tools for studying the pathogenesis of heart failure and identifying new therapeutic targets.

　　In theory, using transgenic technology to overexpress a certain factor in the myocardium, or using gene knockout technology to delete genes closely related to myocardial contractile function, can lead to heart failure. Mouse genes are similar to those of humans and are easily altered, and the altered gene expression is relatively stable. By using gene knock-in, knockout, and interference techniques to alter the expression of heart specific genes, a mouse gene modified heart failure model can be established.

　　【 Model characteristics 】 Muscle lim protein gene knockout mice: Muscle lim protein (MLP) regulates muscle differentiation. Homozygous mice that eliminate the MLP gene will exhibit phenotypes similar to dilated cardiomyopathy, with myocardial hypertrophy, interstitial cell proliferation, and fibrosis. They will develop into HF in adulthood, with hemodynamic and clinical signs similar to human HF. Its characteristic is left ventricular dysfunction and death. Muscle lim protein gene knockout mice have been used as a genetic model for heart failure in many laboratories to explore molecular therapy methods for heart failure and dilated cardiomyopathy.

　　Calmodulin kinase II (CaMK II) transgenic mice showed a significant increase in activity and expression in heart failure. By overexpressing the cytoplasmic subtype of CaMK II in the hearts of transgenic mice, left ventricular hypertrophy and dilation can be observed, gradually progressing to heart failure.

　　Actin gene transgenic mice: Actin gene transgenic mice (mActin Tg, a mutated gene reported in patients with dilated cardiomyopathy) gradually dilate and dysfunction the left ventricle of small and medium-sized mice, ultimately leading to death due to heart failure.

　　Transgenic mice with 1-aminocyclopropane-1-carboxylate synthetase 1: Using the myosin heavy chain gene promoter to overexpress 1-aminocyclopropane-1-carboxylate synthetase 1 in the heart of transgenic mice can establish a metabolic cardiomyopathy mouse model.

　　【 Model evaluation and application 】 Muscle lim protein gene knockout mice as a genetic model for heart failure can be used to explore molecular therapy methods for heart failure and dilated cardiomyopathy. The transgenic mouse model of 1-aminocyclopropane-1-carboxylate synthase 1 can serve as a HF model for lipid metabolism abnormalities, which helps to elucidate the cellular mechanism of lipid toxic HF and provides a research model for pharmacological experiments and gene rescue strategies. Transgenic heart failure models can also be used to understand genes related to heart failure and provide evidence for gene therapy. Its disadvantage is that it cannot comprehensively reflect the true etiology and pathological situation of heart failure patients in clinical practice.