肾上腺髓质素2在肾性高血压大鼠心肌中的变化

目的：通过观察小分子生物活性肽肾上腺髓质素2在大鼠两肾一夹术后肾性高血压发生、发展过程中的变化，探讨其在病理、生理过程中的作用。方法清洁级雄性SD大鼠18只，体重180~220g，随机分为模型组和对照组。模型组行两肾一夹手术，对照组仅分离肾动脉，8周后作左心导管插管法测定血流动力学指标，并计算左室重量与体重比值；采用逆转录-聚合酶链反应方法测定心肌肾上腺髓质素2的mRNA含量变化；采用免疫组织化学方法测定左心室心肌组织的肾上腺髓质素2表达，并对表达强度进行半定量分析。结果模型组大鼠颈动脉收缩压、平均颈动脉压、LV±dp/dtmax、LVEDP较对照组明显升高（P均〈0.01），左室重量与体重也升高（P〈0.05）；模型组大鼠左室心肌肾上腺髓质素2的mRNA表达较对照组高（P〈0.01），免疫组化的累积光密度较对照组升高95%（P〈0.01），且主要发布在心肌细胞的细胞核。结论肾上腺髓质素2在肾性高血压大鼠的心肌内基因表达上调及蛋白合成增加，提示其在肾性高血压致心肌肥厚的过程中起重要作用。

Aim To study the changes and probable role of intermedin/adrenomedullin 2（IMD/ADM2）,a novel micromolecular bioactive peptide,in rats with Two-kidney,One-clip renal hypertension. Methods Eighteen healthy male Sprague-Dawley（SD）rats（180~220g）were randomly divided into normal control group and model group. The rats of model group were cliped with one renal artery,and the contral group only separation one renal artery. After 8 weeks,the left carotid artery was cannulated with a catheter and connected to apressure transducer to monitor the SBP,DBP,mCAP,LVEDP and LV±dp/dtmax. Meanwhile,the LVM/BW was also measured. IMD/ADM2 mRNA expressed in the left ventricular heart muscles were studied with reverse transcription-polymerase chain reaction（RT-PCR）. The location and distribution were detected in the left ventricular heart muscles by using immunohistochemical（IHC）,and semiquantitative analysis was performed in positive regions by using special software-Image Pro Plus（IPP）. Results The systolic blood pressure,mean carotid artery pressure,maximum left ventricular developed pressure increase or decreased rate（±dp/dtmax）and LVEDP of 2K1C group were higher than those of normal control group significantly（all P〈0.01）;The LVM/BW of 2K1C group were higher than those of normal control group（P〈0.05）;The expression of IMD/ADM2 mRNA of the model group were increased（P〈0.01）comparing to control group in the left ventricular organization respectively. The cumulative light density of IMD/ADM2 in the left ventricular organization showed that the model group was higher（P〈0.01）than control group,and the main expression of IMD/ADM2 in myocardial issues were cell nuclei,inflammatory cells. Conclusion These results confirm IMD/ADM2 played an important role in the process of renal hypertension by the mRNA expression and the cumulative light density of IMD/ADM2 are increased In the left ventricular heart muscles of the renal Hypertension rats.