Genetic engineering animal model of catecholamine action system
Catecholamines include epinephrine, norepinephrine, and dopamine and their metabolites. The action system of this kind of substance includes this kind of substance and its action receptor, as well as the action substance in the transformation process of this kind of substance. At present, genes related to hypertension in the action system of such substances are found to be tyrosine hydroxylase, adrenergic receptor and dopamine receptor.
1.β2 adrenergic receptor gene knockout mice
Α2 adrenergic receptor is of great significance in regulating the release of neurotransmitter in the central and peripheral sympathetic nervous system. It mainly inhibits sympathetic nerves. Knockout of this receptor gene enhances the activity of sympathetic nerves and produces hypertension. The polymorphism of the β2 adrenergic receptor gene has a certain correlation with human hypertension. β2 adrenergic receptor gene knockout mice have normal blood pressure, but exercise or adrenaline administration leads to changes in vascular tone and energy metabolism, which further leads to the occurrence of hypertension. This experimental study showed that abnormal β2 adrenergic receptors cannot directly cause essential hypertension (model source: Department of Pediatrics, Georgetown University Medieal Center, Washington, DC 20007, USA).
2. D receptor knockout mice
Kidney dopamine and the renal neuroendocrine system participate in the regulation of sodium excretion to regulate blood pressure. Dopamine receptors are divided into two subgroups: D1 and D2. D1 receptors are further divided into D1 and D5. These receptors are coupled with activating G protein receptors to activate adenylate cyclase; D2 Receptors are divided into D2, D3 and D4 subgroups. These receptors are coupled with inhibitory G protein receptors to inhibit adenylate cyclase activity and calcium channel activity, and also have the effect of regulating potassium channels. Studies have shown that any type of animal model of dopamine receptor gene knockout produces high blood pressure. Both systolic blood pressure and diastolic blood pressure of D1 receptor knockout mice increased significantly, and the natriuretic and diuretic ability of the kidneys of this type of model decreased. The increase in blood pressure in D2 receptor knockout mice is mainly due to the decreased ability of sympathetic nerve excitability inhibition and the enhanced endothelin receptor (ETB2) activity to produce high blood pressure, but its urinary sodium excretion function is enhanced, and the sodium transport pump activity is reduced. Increased blood pressure in D3 receptor knockout mice is related to abnormal renin angiotensin aldosterone system. Stimulating D3 receptors in paraglomerular cells can inhibit the protein and mRNA expression of AT1 receptors in renal proximal tubules of renin. The increase in blood pressure of D4 receptor knockout mice may be related to AT1 receptor. Both the systolic and diastolic blood pressures of D5 receptor knockout were significantly increased, and under the condition of high-salt diet, their blood pressure further increased, indicating that the kidney dysfunction of mice plays a certain role in the mechanism of blood pressure increase. The abnormal interaction between stress and AT1 receptor is involved in the occurrence and development of hypertension. The five types of dopamine receptor gene knockout mice all produce hypertension, suggesting the important role of dopamine receptors in regulating blood pressure. The establishment of these models is of great significance for studying the pathogenesis of different types of dopamine receptors in hypertension.
动物模型
z-bo
2020-08-11
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