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目的:探讨肾上腺髓质素(AM)受体系统在恶性高血压大鼠肾脏中的病理生理作用及利尿剂的干预作用。方法:实验分3组:Wistar-Kyoto大鼠(WKY)为对照组,有卒中倾向的自发性高血压大鼠组(SHR-SP),用三氯甲噻嗪治疗8周组(SHR-SP+Diuretic)。通过放射性免疫分析,检测AM受体系统如降钙素受体类似受体(CRLR),受体活性修饰蛋白(RAMP)2和RAMP3的基因表达水平。结果:SHR-SP组血压,血中神经体液因子均较WKY组有所升高,而肾功能有所降低。肾脏的皮质中CRLR,RAMP2,RAMP3的 mRNA水平显著高于WKY组。长期的利尿治疗能降低血压,伴随血液和肾脏组织中AM受体系统降低而改善肾功能,提高神经体液因子浓度。结论:在循环血液和肾脏组织中,AM受体系统的上调可能参与恶性高血压大鼠的病理生理过程,利尿剂可以下调AM受体。
Objective: To investigate the pathophysiological effects of adrenomedullin (AM) receptor system in the kidney of rats with malignant hypertension and the intervention of diuretics. Methods: The experiment was divided into three groups: Wistar-Kyoto rats (WKY) as control group, SHR-SP group with stroke predisposition, SHR-SP group + Diuretic). Radioimmunoassay was used to detect gene expression levels of AM receptor systems such as calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP) 2 and RAMP3. Results: The blood pressure and blood humoral factors in SHR-SP group were higher than those in WKY group, while the renal function was decreased. The mRNA levels of CRLR, RAMP2 and RAMP3 in the kidney cortex were significantly higher than those in the WKY group. Long-term diuretic therapy can lower blood pressure, improve renal function and lower the concentration of neurohumoral fluid with the decrease of AM receptor system in blood and kidney tissues. CONCLUSION: Upregulation of AM receptor system may be involved in the pathophysiological process of malignant hypertensive rats in circulating blood and kidneys, and diuretics may down-regulate AM receptors.