肾上腺髓质素及其受体系统抑制溶血磷脂酸诱导的大鼠主动脉平滑肌细胞增殖

Adrenomedullin with Its Receptor Inhibit the Proliferation of Vascular Smooth Muscle Cells in Rats Induced by Lysophosphatidic Acide

目的观察溶血磷脂酸对肾上腺髓质素及其受体系统生成的影响和肾上腺髓质素在溶血磷脂酸促进血管平滑肌细胞增殖中的作用。方法贴块法培养大鼠胸主动脉血管平滑肌细胞,H3-TdR掺入测定血管平滑肌细胞DNA合成,γ-32P-ATP标记的同位素法测定丝裂原活化蛋白激酶活性,放射免疫法测定血管平滑肌细胞中肾上腺髓质素的含量。结果溶血磷脂酸促进大鼠血管平滑肌细胞肾上腺髓质素生成,上调血管平滑肌细胞肾上腺髓质素及其受体CRLR、RAMP2和RAMP3mRNA表达;肾上腺髓质素可抑制溶血磷脂酸刺激大鼠血管平滑肌细胞3H-TdR掺入,抑制溶血磷脂酸诱导的丝裂原活化蛋白激酶激活。结论溶血磷脂酸上调血管平滑肌细胞肾上腺髓质素及其受体系统,肾上腺髓质素及其受体抑制血管平滑肌细胞增殖的作用与其抑制丝裂原活化蛋白激酶激活有关。

Aim To observe the effects of lysophosphatidic acid （IPA） on system generation of adrenomedullin （ADM） with its receptors： calcitonin receptor like receptor （CRLR） and receptor activity modifying protein （RAMP）, and the effects of ADM on proliferation of the vascular smooth muscle cells （VSMC） induced by LPA. Methods VSMC of rat aortic were cultured by explant method. DNA synthesis of VSMC were measured by ^3H-TdR incorporation. The ADM concentration in VSMC were determined by radioimmunoassay, Results IPA stimulated the production of ADM on vascular smooth muscle cells in rats, IPA up-regulated the expression of nLR.NA of ADM and its receptors CRLR, RAMP2 and RAMP3 in VSMC. ADM can inhibit ^3H-TdR incorporation of rat VSMC stimulated by IPA. ADM inhibited activation of mitogen-activated protein kinase （MAPK） in VSMC induced by IPA, Conclusions ADM and its receptors inhibit VSMC proliferation which involves in its inhibition on MAPK activity.