摘要
目的：观察长期给予二甲双胍对盐敏感性高血压大鼠下丘脑室旁核（PVN）区炎症水平、氧化应激水平、交感神经活性及血压的影响，探讨其对盐敏感性高血压的中枢干预机制。方法选取8周龄雄性Dahl 盐敏感大鼠24只，随机分为四组，每组6只，分别为正常对照组（0．3％氯化钠溶液＋侧脑室输注人工脑脊液）、正常给药组（0．3％氯化钠溶液＋侧脑室输注二甲双胍25μg／d）、高盐对照组（8％氯化钠溶液＋侧脑室输注人工脑脊液）及高盐给药组（8％氯化钠溶液＋侧脑室输注二甲双胍25μg／d）。通过鼠尾动脉血压测量系统记录其血压变化。干预6周后，麻醉后处死动物并提取 PVN 组织及血浆，采用 ELISA 检测各组大鼠血浆去甲肾上腺素（NE）水平（评价交感神经活性的间接指标）；采用免疫荧光染色法、免疫组化、蛋白免疫印迹法检测 PVN 区白细胞介素（IL）-1β、IL-10以及 NAD（P）H 氧化酶亚基 NOX-2、过氧化物歧化酶（SOD）水平，超氧化物阴离子荧光探针（DHE）染色观察 PVN 区活性氧簇（ROS）的变化。结果高盐给药组与高盐对照组相比平均动脉压（MAP）降低[第6周：（129．55±6．52）mmHg 比（154．47±6．57）mmHg，F ＝121．90，P ＜0.05]；高盐给药组与高盐对照组相比血浆 NE 水平降低[（364．57±30．73）pg／mL 比（547．68±25．08）pg／mL， F ＝179．24，P ＜0．05]；高盐给药组 PVN 区 IL-1β、IL-6、NOX-2和 ROS 表达较高盐对照组降低（F ＝27．80、21.20、22．48、31．99，均 P ＜0．05），IL-10和 SOD 水平较高盐对照组升高（F ＝17．69、23．69，均 P ＜0．05）。结论二甲双胍能够降低高盐喂食导致的盐敏感大鼠 PVN 区炎症水平并减弱氧化应激，进而抑制交感神经兴奋，降低平均动脉压。
Objective To explore central mechanism of metformin（MET）in salt -sensitive hypertensive rats by assessing the effect of metformin on inflammation and oxidative stress in hypothalamic paraventricular nucleus （PVN）,sympathetic nerve activity and blood pressure.Methods Eight -week -old male Dahl salt -sensitive rats were divided into 4 groups：the normal -salt diet control group[0.3% NaCl ＋intracerebroventricular（ICV）artificial cerebrospinal fluid（aCSF）],the normal -salt diet with MET group（0.3% NaCl ＋ICV MET 25μg/d],the high -salt diet control group （8% NaCl ＋ICV aCSF）,the high -salt diet with MET group （8% NaCl ＋ICV MET 25μg/d）. Mean arterial pressure（MAP）was determined every week by a tail -cuff occlusion.After 6 weeks,all rats were eutha-nized,and blood and brain tissues were collected.Then,the plasma norepinephrine（NE,an indicator of sympathetic activity）was detected by enzyme linked immune sorbent assay（ELISA）.The expression levels of interleukin（IL）-1β,IL -10 and NOX -2[a subunit of NAD（P）H oxidase],superoxide dismutase（SOD）in the PVN were detected by immunofluorescence,immunohistochemistry and Western blot methods.Reactive oxygen species（ROS）was detec-ted by dihydroethidium（DHE）staining.Results The MAP level of high -salt diet with metformin group was attenu-ated compared with that of the high -salt diet control group[（129.55 ±6.52）mmHg vs.（154.47 ±6.57）mmHg, F =121.90,P 〈0.05].The change of plasma NE level of high -salt diet with metformin group was lower compared with that of the high -salt diet control group[（364.57 ±30.73）pg/mL vs.（547.68 ±25.08）pg/mL,F =179.24, P 〈0.05].The expression levels of IL -1β,IL -6,NOX -2 and ROS were markedly higher in high -salt diet with metformin than those of the high -salt diet control group（F =27.80,21.20,22.48,31.99,all P 〈0.05）,which of IL -10 and SOD was lower（F =17.69,23.69,all P 〈0.05）.Conclusion Metformin may attenuate blood pressure in salt -sensitive hypertensive rats,at least partly via decreasing inflammatory molecules and inhibiting oxidative stress in the PVN,subsequently inhibiting sympathoexcitation.
出处
《中国基层医药》
CAS
2016年第14期2189-2193,共5页
Chinese Journal of Primary Medicine and Pharmacy
关键词
高血压
二甲双胍
下丘脑室旁核
炎症
氧化应激
Hypertension
Metformin
Hypothalamic paraventricular nucleus
Inflammation
Oxida-tive stress
