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目的探讨G蛋白激酶(GRK)4γ变异体A142V转基因小鼠血压升高的原因,以期了解GRK4γ在调控血压中的作用。方法以GRK4γA142V转基因小鼠为研究对象,分别对其血压、肾脏尿钠排泄功能、D1多巴胺受体的表达进行测定;并应用GRK4反义核苷酸技术处理HK-2细胞,研究在GRK4表达受到抑制的情况下D1受体的表达变化。结果与对照小鼠相比,GRK4γA142V转基因小鼠血压明显增高,肾脏D1受体介导的利尿、利钠作用明显下降,伴有肾脏皮质膜D1受体表达降低(0.6±0.2比1.5±0.2,n=3)、磷酸化程度增高[(65±7)DU比(35±7)DU,n=3];反义核苷酸抑制GRK4(1.2±0.1比1.3±0.1比0.6±0.1,n=6)表达后,D1受体的表达量增高(0.7±0.1比0.8±0.1比1.5±0.2,n=6),说明D1受体功能下降是GRK4γA142V转基因小鼠血压升高的原因。结论GRK4γ与高血压的发生关系密切,GRK4γA142V转基因小鼠血压升高与肾脏D1受体功能下降有关。
Objective To investigate the reason of elevated blood pressure in A142V transgenic mice with G protein kinase (GRK) 4γ mutation in order to understand the role of GRK4γ in the regulation of blood pressure. Methods GRK4γA142V transgenic mice were used as experimental subjects, and their blood pressure, renal excretion of urinary sodium and the expression of D1 dopamine receptor were measured respectively. HK-2 cells were treated with GRK4 antisense oligonucleotide to study the effect of GRK4 on GRK4 expression D1 receptor expression in the absence of inhibition. Results Compared with the control mice, the GRK4γA142V transgenic mice showed significantly higher blood pressure, significantly decreased the diuretic and natriuresis mediated by D1 receptor, and decreased the expression of D1 receptor in the renal cortex (0.6 ± 0.2 vs. 1.5 ± 0.2, (65 ± 7) DU (35 ± 7) DU, n = 3]; antisense nucleotide inhibited GRK4 (1.2 ± 0.1 vs 1.3 ± 0.1 vs 0.6 ± 0.1, n = 6), the expression of D1 receptor increased (0.7 ± 0.1 vs 0.8 ± 0.1 vs 1.5 ± 0.2, n = 6), indicating that the decrease of D1 receptor function was responsible for the increase of blood pressure in GRK4γA142V transgenic mice. Conclusion GRK4γ is closely related to the occurrence of hypertension. The increase of blood pressure in GRK4γA142V transgenic mice is related to the decline of renal function of D1 receptor.