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背景尼克酰胺腺嘌呤二核苷酸磷酸[NAD(P)H]氧化酶产生的超氧阴离子在高血压病的发生、发展中发挥了重要作用。AngⅡ灌注可增高大脑NAD(P)H氧化酶的活性,这种增高效应可分别被坎地沙坦和NAD(P)H氧化酶抑制剂所抑制,表明氧化应激可能在原发性高血压所致的大脑损伤中发挥重要作用。除了降压作用外,血管紧张素Ⅱ受体拮抗剂(ARB)防治高血压脑卒中的作用机制尚未完全阐明。目的探讨ARB类药物坎地沙坦对盐负荷易卒中自发性高血压大鼠(SHRsp)大脑NAD(P)H氧化酶基因表达的影响。方法将12周龄喂饲8%高盐饮食的SHRsp大鼠随机分为3组:坎地沙坦组[1.0mg/(kg.d),n=12];三氯噻嗪组[1.6mg/(kg.d),n=12];SHRsp组(n=12),予等量溶媒。相同喂饲条件的WKY(WistarKyoto)大鼠作为对照组(n=12)。每周测量血压。给药2周后,用ELISA法测定24h尿白蛋白;摘取大脑标本,见肉眼可识别的出血灶/梗死灶,记录各组脑卒中发生数;采用实时定量PCR检测大脑皮质NAD(P)H氧化酶亚单位mRNA表达。结果SHRsp组收缩压明显高于WKY组,予坎地沙坦和三氯噻嗪后,两组收缩压均下降(P<0.01),下降幅度无明显差别。SHRsp组尿白蛋白排泄及大脑皮质NAD(P)H氧化酶亚单位mRNA表达明显高于WKY组。坎地沙坦降低尿白蛋白,下调大脑皮质NAD(P)H氧化酶亚单位mRNA的表达(P<0.01),降低了脑卒中发生率(P<0.05),而等效利尿剂三氯噻嗪对大脑皮质NAD(P)H氧化酶亚单位表达和脑卒中发生率无明显影响。结论坎地沙坦对盐负荷SHRsp大脑的保护作用,除降压作用外,尚与抑制NAD(P)H氧化酶有关。
Background Nickel amide adenine dinucleotide phosphate [NAD (P) H] oxidase superoxide anion in the occurrence and development of hypertension plays an important role. Ang Ⅱ infusion increased brain NAD (P) H oxidase activity, which was inhibited by candesartan and NAD (P) H oxidase inhibitors, respectively, indicating that oxidative stress may be associated with primary hypertension Caused by brain damage play an important role. In addition to antihypertensive effects, the mechanism by which angiotensin II receptor antagonists (ARBs) prevent and treat hypertensive stroke has not been fully elucidated. Objective To investigate the effect of candesartan on the gene expression of NAD (P) H oxidase in the brain of spontaneously hypertensive rats (SHRsp) with saline-loaded stroke. Methods SHRsp rats aged 12 weeks and fed with 8% salt diet were randomly divided into 3 groups: candesartan group [1.0 mg / (kg · d), n = 12], trichlormethazine group [1.6 mg /(kg.d),n=12]SHRsp group (n = 12), given the same amount of vehicle. WKY (Wistar Kyoto) rats of the same feeding conditions were used as a control group (n = 12). Measure blood pressure weekly. After 2 weeks of administration, urinary albumin was measured 24h by ELISA; brain samples were taken out, and the number of cerebral hemorrhage / infarction identified by naked eyes was recorded. The number of cerebral apoplexy in each group was recorded. NAD (P) H oxidase subunit mRNA expression. Results The systolic blood pressure of SHRsp group was significantly higher than that of WKY group (P <0.01). After treatment with candesartan and trichlormethiazide, the systolic blood pressure of both groups decreased (P <0.01). There was no significant difference between the two groups. Urinary albumin excretion and NAD (P) H oxidase subunit mRNA expression in SHRsp group were significantly higher than those in WKY group. Candesartan decreased urinary albumin and down-regulated the expression of NAD (P) H oxidase subunit mRNA in the cerebral cortex (P <0.01), reduced the incidence of stroke (P <0.05), whereas the equivalent diuretic There was no significant effect of oxazine on NAD (P) H oxidase subunit expression and stroke incidence in cerebral cortex. Conclusion The protective effect of candesartan on the salt-loaded SHRsp brain is related to inhibition of NAD (P) H oxidase in addition to the hypotensive effect.