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目的探讨来自同一前体的肾上腺髓质素(ADM)及肾上腺髓质素N末端20肽(PAMP)在高肺血流肺动脉高压形成中的变化及作用途径。方法健康雄性Wistar大鼠21只,随机分为2组。将实验组(n=9)大鼠的左侧颈总动脉与颈外静脉用套管进行连接,对照组大鼠仅切开颈部皮肤分别分离颈总动脉和颈外静脉后缝合皮肤,不进行血管连接术。术后12周,经右心导管测取大鼠肺动脉平均压(mPAP)、右心室/(室间隔+左心室)(RV/(LV+SP))重量比、中等肺动脉壁厚度所占管径百分比(MT%)。免疫组化法和Western blotting测定ADM、PAMP在大鼠肺组织中的分布及其相对含量变化。RT-PCR法检测大鼠肺组织中ADM、应力活化蛋白激酶(SAPK)、细胞外信号调节激酶(ERK1)基因表达量。结果实验组大鼠术后mPAP与对照组比较明显升高(P<0.001);RV/(LV+SP)和MT%比例明显增加(P<0.001和P<0.01)。免疫组化结果显示ADM和PAMP棕色颗粒主要分布于血管平滑肌层;累积光密度(OD)及Western blotting结果显示实验组大鼠肺内ADM及PAMP蛋白表达量增加。RT-PCR结果显示实验组大鼠肺组织ADM、SAPK、ERK1mRNA与对照组比较表达增强(P<0.01,P<0.001)。结论高肺血流肺动脉高压形成中存在来自同一前体的ADM与PAMP之间的分子内调控现象;丝裂原活化蛋白激酶(MAPKs)信号通路可能参与了高肺血流肺动脉高压形成过程。
Objective To investigate the changes of adrenomedullin (ADM) and adrenomedullin N-terminal 20 peptide (PAMP) from the same precursor in the formation of pulmonary hypertension in patients with pulmonary hypertension. Methods Twenty-one healthy male Wistar rats were randomly divided into two groups. The left common carotid artery and external jugular vein in the experimental group (n = 9) rats were connected by cannula. In the control group, only the common skin of the neck was excised, the common carotid artery and external jugular vein were separated, and the skin was not sutured. Vascular surgery. At 12 weeks after operation, the mean pulmonary arterial pressure (mPAP), right ventricular (RV / (LV + SP)) weight ratio, middle pulmonary artery wall thickness Percentage (MT%). Immunohistochemistry and Western blotting were used to determine the distribution and relative content of ADM and PAMP in rat lung tissue. The expression of ADM, stress-activated protein kinase (SAPK) and extracellular signal-regulated kinase (ERK1) in rat lung tissue were detected by RT-PCR. Results The mPAP in experimental group was significantly higher than that in control group (P <0.001). The ratio of RV / (LV + SP) and MT% increased significantly (P <0.001 and P <0.01). Immunohistochemistry showed that brown granules of ADM and PAMP mainly distributed in vascular smooth muscle layer. The OD value and Western blotting results showed that the expression of ADM and PAMP protein in lung increased in experimental group. The results of RT-PCR showed that the expressions of ADM, SAPK and ERK1 mRNA in the lung tissue of experimental group were significantly increased compared with the control group (P <0.01, P <0.001). Conclusions There is an intramolecular regulation of ADM and PAMP in the formation of pulmonary hypertension with high pulmonary blood flow. Mitogen-activated protein kinase (MAPKs) signaling pathway may be involved in the process of pulmonary hypertension with pulmonary hypertension.