姜黄素对长期高盐诱导高血压大鼠中枢的作用机制

Central mechanism of curcumin on the paraventricular hypothalamic nucleus of high salt induced hypertension rats

目的:探讨姜黄素对长期高盐诱导的高血压大鼠下丘脑室旁核的影响,并探讨其作用机制。方法:选取健康雄性Dahl大鼠60只,体质量(180±10)g,随机分为4组,每组15只,分别为正常饮食对照组(含0.3%NaCl)、正常饮食给药组(0.3%NaCl+姜黄素150 mg·kg^(-1)·d^(-1))、高血压组(含8%NaCl)以及高血压治疗组(8%NaCl+姜黄素150 mg·kg^(-1)·d^(-1))。采用无创大鼠尾动脉监测系统测量每组大鼠血压变化。经姜黄素连续灌胃6周后,采用戊巴比妥钠麻醉大鼠,然后处死大鼠提取下丘脑室旁核组织和血浆,采用RT-PCR、ELISA、免疫荧光检测下丘脑室旁核中NAD(P)H氧化酶亚基NOX2、NOX4、过氧化物歧化酶(SOD-1)、Toll样受体(toll-like receptor,TLR4)、髓样分化因子(myeloid differentiation factor 88,MyD88)、白细胞介素6(IL-6)、IL-1β、MCP-1及IL-10指标的RNA及细胞水平,采用DHE法检测下丘脑室旁核活性氧簇的变化。结果:高盐饮食组大鼠经过6周姜黄素干预后平均动脉血压明显降低[6周时:(125+7)mmHg比(153+6)mmHg,P<0.05];长期高盐饮食组大鼠经姜黄素干预后NOX2、NOX4、TLR4、MyD88、IL-6、IL-1β、MCP-1及ROS水平明显较高盐饮食组降低(P<0.05),而SOD-1和IL-10表达明显较高盐饮食组升高(P<0.05)。结论:姜黄素能够改善长期高盐诱导的高血压大鼠血压,其机制可能与改善下丘脑室旁核中氧化应激和炎症细胞因子有关。

AIM:To assess the effect of curcumin in hypothalamic paraventricular nucleus(PVN)and mean arterial pressure so as to explore the central mechanism of hypertension.METHODS:Sixty Sprague-Dawley rats which body weights between 170 and 190 grams fed with a normal salt(0.3%Na-Cl)or a high salt(8%NaCl)diet for 6 weeks.Mean-while half of each team received curcumin adminis-tration or vehicle by intragastric administration.Mean Arterial pressure was measured noninvasive-ly via tail-cuff instrument and their recording sys-tem.The PVN tissue samPles were collected and stored at-80°C for later analyses.We performed the following experimental procedures:Western blot analysis,immunofluorescence,immunofluores-cence and statistical analysis.RESULTS:The aver-age arterial blood Pressure of rats in the high-salt diet group was significantly reduced after 6 weeks of curcumin intervention.The levels of NOX2,NOX4,TLR4,MyD88,IL-6,IL-1β,MCP-1 and ROS in the long-term high-salt diet grouP were significant-ly higher after curcumin intervention.CONCLU-SION:Curcumin can improve blood pressure in hy-pertensive rats induced by long-term high salt,the mechanism may be related to the imProvement of oxidative stress and inflammatory cytokines in the paraventricular nucleus of the hypothalamus.