【摘要】 目的探讨血管紧张素Ⅱ-CaMK-CREB-CYP11B2和肾上腺素-PKA-CREB-CYP11B2途径在应激性高血压(SIH)发病中的作用。方法选取鼠龄在6～8w的SPF级雄性Wistar大鼠28只,适应性喂养7d后,按照完全随机法分为SIH模型组与正常组,每组14只。通过每天声光间断足底电、夹尾持续刺激12w构建SIH大鼠模型。采用放射免疫法检测SIH模型大鼠血浆血管紧张素Ⅱ含量,酶联免疫吸附(ELISA)方法检测SIH模型大鼠血清肾上腺素含量,实时荧光定量PCR(RT-qPCR)和免疫组织化学方法检测SIH模型大鼠肾上腺组织Creb、Nr4a1、Nr4a2、Cyp11b2基因mRNA表达和环磷酸腺苷反应元件结合蛋白(CREB)磷酸化水平及醛固酮合酶(CYP11B2)蛋白表达水平的变化。结果与正常组比较,SIH模型组大鼠体质量增长明显缓慢,收缩压与舒张压均明显升高(P <0.05),血浆血管紧张素Ⅱ含量无明显变化(P>0.05),血清肾上腺素含量明显升高(P <0.05),肾上腺组织Creb基因mRNA表达水平明显上调(P <0.05),Nr4a1与Nr4a2基因mRNA表达水平有下调趋势(P>0.05),Cyp11b2基因mRNA表达水平明显上调(P <0.05);与正常组比较,SIH模型组大鼠肾上腺CREB磷酸化水平及CYP11B2蛋白表达水平明显上调(P <0.05)。结论SIH模型组大鼠肾上腺组织肾上腺素-PKA-CREBCYP11B2途径的激活是血液醛固酮含量增多、应激性高血压发病的原因之一。更多还原

【Abstract】 Objective To investigate the role of the angiotensin Ⅱ-CaMK-CREB-CYP11B2 and adrenergic-PKACREB-CYP11B2 pathways in the pathogenesis of stress induce hypertension(SIH).Methods Aged 6-8weeks of28 male SPF Wistar rats were randomly divided into SIH model group and normal group,with 14 rats in each group.The SIH rat model was constructed by daily sound and light interruption of the foot and continuous stimulation of the tail for 12 weeks.The content of plasma angiotensin Ⅱ in SIH model rats were detected by radioimmunoassay.The serum adrenaline contents in SIH model rats were examined by ELISA.The mRNAs of Creb,Nr4a1,Nr4a2 and Cyp11b2genes,the changes of CREB phosphorylation levels and CYP11B2 protein expression levels in adrenal tissue of SIH model rats were detected by RT-qPCR and immunohistochemistry,respectively.Results Compared with the normal group,the speed of body mass growth in SIH model group was significantly slower and the systolic blood pressure and diastolic blood pressure were significantly increased(P <0.05).Compared with the normal group,the content of plasma angiotensin Ⅱ in the SIH model group was not changed(P >0.05),but the content of serum adrenaline was significantly increased(P <0.05),and adrenal tissue Creb gene mRNA expression level and the level of Cyp11b2 mRNA were significantly up-regulated(P <0.05).Though Nr4a1 and Nr4a2gene mRNA expression levels were down-regulated,there was no statistical significance(P >0.05).Compared with the normal group,the phosphorylation level of CREB and the expression of CYP11B2 protein in the SIH model group were significantly up-regulated(P <0.05).Conclusion The activation of the adrenal-PKACREB-CYP 11B2 pathway in stress-induced hypertension group is the main cause of increased blood aldosterone content and onset of stress-induce hypertension.更多还原