NADPH氧化酶Nox4调控非诺贝特的抗高血压心肌肥大效应

目的拟阐明NADPH氧化酶Nox4与非诺贝特抗高血压心肌肥大效应的关系。方法构建腹主动脉缩窄(abdominal aorta coarctation,AAC)诱导的高血压大鼠模型,观察非诺贝特对高血压大鼠左心室肥大的影响。结果非诺贝特可显著抑制AAC高血压大鼠左心室肥大。与假手术组比较,AAC组左心室中NADPH氧化酶Nox4蛋白和mRNA水平均显著增加;与AAC组比较,非诺贝特剂量依赖性降低AAC高血压大鼠左心室中NADPH氧化酶Nox4蛋白和mRNA水平。结论降低NADPH氧化酶Nox4表达可能是非诺贝特发挥抗高血压心肌肥大效应的重要机制。     

Prostanoid-mediated contractions of the carotid artery become Nox2-independent with aging

Aging is a major risk factor for carotid artery disease that may lead to stroke and dementia. Vascular effects associated with aging include increased vasomotor tone, as well as enhanced contractility to endothelial vasoconstrictor prostanoids and reduced nitric oxide (NO) bioactivity partly due to increased oxidative stress. We hypothesized that vascular NADPH oxidase (Nox)-derived superoxide may be involved in prostanoid- and NO-related functional aging. NO-mediated relaxations and prostanoid-mediated contractions to acetylcholine as well as phenylephrine-dependent contractions were investigated in the carotid artery from young (4 months) and aged mice (24 months). Gene expression of Nox subunits and endothelial NO synthase (eNOS) was determined in the carotid artery and aorta. In young mice, the thromboxane-prostanoid receptor antagonist SQ 29,548 fully blocked acetylcholine-induced contractions while reducing responses to phenylephrine by 75 %. The Nox2-targeted inhibitor Nox2ds-tat and the superoxide scavenger tempol reduced acetylcholine-stimulated, prostanoid-mediated contractions by 85 and 75 %, respectively, and phenylephrine-dependent contractions by 45 %. Unexpectedly, in aged mice, the substantial Nox2-dependent component of acetylcholine- and phenylephrine-induced, prostanoid-mediated contractions was abolished. In addition, endothelium-dependent, NO-mediated relaxations were impaired with aging. The expression of Nox subunits was greater in the aorta compared with the carotid artery, in which Nox1 was undetectable. eNOS gene expression was reduced in the aorta of aged compared to young mice. In conclusion, aging decreases prostanoid-mediated contractility in the carotid artery involving a loss of Nox2 activity and is associated with impaired endothelium-dependent, NO-mediated relaxation. These findings may contribute to a better understanding of the pathophysiology of carotid artery disease and the aging process.     

Activation of apocynin-sensitive NADPH oxidase (Nox2) activity in INS-1 832/13 cells under glucotoxic conditions

Several lines of recent evidence provided compelling evidence to suggest increased generation of reactive oxygen species (ROS) as causal for mitochondrial dysregulation and apoptosis in islet β-cells exposed to noxious stimuli including high glucose, lipids and proinflammatory cytokines. Studies along these lines are also suggestive of a significant contributory role for NADPH oxidase in the generation of ROS under the above conditions. We have recently reported a marked increase in the expression and activation of cytosolic components of NADPH oxidase (p47phox, Rac1) in cell culture models of glucotoxicity and in islets from T2DM animals (Zucker Diabetic Fatty rat) and humans. In this communication, we provide further evidence indicating significant activation of NADPH activity (~2-fold) in INS-1 832/13 cells exposed to chronic hyperglycemic conditions (20 mM; 48 h). We also report marked attenuation of this activity, by apocynin, a selective inhibitor of phagocyte-like NADPH oxidase (Nox2) activity. Together, our findings implicate Nox2 as a source for ROS generation in β-cells exposed to glucotoxic conditions.     

Opportunity Nox: The Future of NADPH Oxidases as Therapeutic Targets in Cardiovascular Disease

Over 40 years ago, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (Nox2) was discovered in phagocytes and found to be essential in innate immunity. More than 20 years passed before additional Nox isoforms were discovered; and since then, studies have revealed that several of these isoforms (Nox1, Nox2, Nox4, and Nox5) are found in human cardiac and vascular cells and contribute to the pathogenesis of cardiovascular diseases (CVDs). Recently, major efforts have focused on identifying inhibitors capable of ameliorating Nox‐mediated CVD. In this review, we briefly discuss the role of each Nox isoform in CVD, identify steps in Nox signaling that will serve as potential targets for the design of therapeutics, and highlight innovative strategies likely to yield effective Nox inhibitors within the next decade.     

尼克酰胺腺嘌呤二核苷酸磷酸氧化酶与心血管疾病关系的研究进展

活性氧的增加与心血管疾病密切相关,而产生活性氧的主要酶体是尼克酰胺腺嘌呤二核苷酸氧化酶(NADPH氧化酶)。NADPH氧化酶对动脉粥样硬化、高血压、心力衰竭的发生发展起着重要的作用;而心房颤动又可引起NADPH氧化酶的增加。     

NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart

NAD(P)H oxidases (Noxs) produce O₂⁻ and play an important role in cardiovascular pathophysiology. The Nox4 isoform is expressed primarily in the mitochondria in cardiac myocytes. To elucidate the function of endogenous Nox4 in the heart, we generated cardiac-specific Nox4^−/− (c-Nox4^−/−) mice. Nox4 expression was inhibited in c-Nox4^−/− mice in a heart-specific manner, and there was no compensatory up-regulation in other Nox enzymes. These mice exhibited reduced levels of O₂⁻ in the heart, indicating that Nox4 is a significant source of O₂⁻ in cardiac myocytes. The baseline cardiac phenotype was normal in young c-Nox4^−/− mice. In response to pressure overload (PO), however, increases in Nox4 expression and O₂⁻ production in mitochondria were abolished in c-Nox4^−/− mice, and c-Nox4^−/− mice exhibited significantly attenuated cardiac hypertrophy, interstitial fibrosis and apoptosis, and better cardiac function compared with WT mice. Mitochondrial swelling, cytochrome c release, and decreases in both mitochondrial DNA and aconitase activity in response to PO were attenuated in c-Nox4^−/− mice. On the other hand, overexpression of Nox4 in mouse hearts exacerbated cardiac dysfunction, fibrosis, and apoptosis in response to PO. These results suggest that Nox4 in cardiac myocytes is a major source of mitochondrial oxidative stress, thereby mediating mitochondrial and cardiac dysfunction during PO.     

NADPH氧化酶在酒精性肝病发病机制中的作用

酒精性肝病（ALD）的发病机制有人提出以氧应激和脂质过氧化为中心的“二次打击”假说，NADPH氧化酶（NADPH oxidase，NOX）与自由基形成有着密切关系，参与ALD的多个环节。     

Dual granule localization of the dormant NADPH oxidase and cytochrome b559 in human neutrophils

The subcellular localization of the microbicidal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and associated b-cytochrome was investigated in human neutrophils. In unperturbed neutrophils 85% of b-cytochrome and the major part of membrane-bound components of the NADPH oxidase co-sedimented with markers for specific granules and gelatinase. Using cytochrome b559 as a marker for membrane-bound components of the NADPH oxidase in quantitative studies we observed that, of the remaining 15%, the vast majority co-sedimented with latent alkaline phosphatase, a marker for a newly identified mobilizable intracellular compartment. Only a small fraction co-localized with the plasma membranes. Azurophil granules contained a protease activity which rapidly inactivated the NADPH oxidase components present in other membranes. Stimulation of the neutrophils with formyl-methionyl-leucyl-phenyl-alanine and leukotriene B4 which caused minimal degranulation of specific granules, resulted in translocation of b-cytochrome to the plasma membrane, concomitant with incorporation of alkaline phosphatase into the plasma membrane.     

NADPH oxidase 2 (NOX2): A key target of oxidative stress-mediated platelet activation and thrombosis

Oxidative stress represents an imbalance between the production of reactive oxygen species (ROS) and the cellular antioxidant system. Increased levels of oxidative stress contribute to the development of atherosclerosis that eventually leads to thrombosis; a principle cause of heart attacks and strokes. Thrombosis is a consequence of platelet activation and aggregate formation within the circulation. Platelet ROS are mostly generated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. NOX2 is an isoform from NADPH oxidase expressed in platelets and an important regulator of platelet activation‐associated thrombosis. The present article aims to highlight the relative contribution of NOX2 as a key target of different platelet activation pathways and antiplatelet treatment.     

Preconditioning protects endothelium by preventing ET-1-induced activation of NADPH oxidase and xanthine oxidase in post-ischemic heart

The hypothesis was tested that endothelin-1 (ET-1)-induced superoxide (O(2)(-)) generation mediates post-ischemic coronary endothelial injury, that ischemic preconditioning (IPC) affords endothelial protection by preventing post-ischemic ET-1, and thus O(2)(-), generation, and that opening of the mitochondrial ATP-dependent potassium channel (mK(ATP)) triggers the mechanism of IPC. Furthermore, the study was aimed at identifying the source of O(2)(-) mediating the endothelial injury. Langendorff-perfused guinea-pig hearts were subjected either to 30 min ischemia/35 min reperfusion (IR) or were preconditioned prior to IR with three cycles of either 5 min ischemia/5 min reperfusion or 5 min infusion/5 min washout of mK(ATP) opener diazoxide (0.5 mM). Coronary flow responses to acetylcholine (ACh) served as a measure of endothelium-dependent vascular function. Myocardial outflow of ET-1 and O(2)(-) and functional recoveries were followed during reperfusion. NADPH oxidase and xanthine oxidase (XO) activities were measured in cardiac homogenates. IR augmented ET-1 and O(2)(-) outflow and impaired ACh response. All these effects were attenuated or prevented by IPC and diazoxide, and 5-hydroxydecanoate (a selective mK(ATP) blocker) abolished the effects of IPC and diazoxide. Superoxide dismutase and tezosentan (a mixed ET-1-receptor antagonist) mimicked the effects of IPC, although they had no effect on the ET-1 generation. IR augmented also the activity of NADPH oxidase and XO. Apocynin treatment, that resulted in NADPH oxidase inhibition, prevented XO activation and O(2)(-) generation in IR hearts. The inhibition of XO, either by allopurinol or feeding the animals with tungsten-enriched chow, prevented post-ischemic O(2)(-) generation, although these interventions had no effect on the NADPH activity. In addition, the post-ischemic activation of NADPH oxidase and XO, and O(2)(-) generation were prevented by IPC, tezosentan, thenoyltrifluoroacetone (mitochondrial complex II inhibitor), and tempol (cell-membrane permeable O(2)(-) scavenger). In guinea-pig heart: (i) ET-1-induced O(2)(-) generation mediates post-ischemic endothelial dysfunction; (ii) IPC and diazoxide afford endothelial protection by attenuating the ET-1, and thus O(2)(-) generation, and the mK(ATP) opening triggers the protection; (iii) the NADPH oxidase maintains the activity of XO, and the XO-derived O(2)(-) mediates the endothelial injury, and (iv) ET-1 and O(2)(-) (probably of mitochondrial origin) are upstream activators of the NADPH oxidase-XO cascade, and IPC prevents the cascade activation and the endothelial dysfunction by preventing the ET-1 generation.     

Nitrite confers protection against myocardial infarction: role of xanthine oxidoreductase, NADPH oxidase and K(ATP) channels

Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia/reperfusion. However the optimal dose of nitrite and the mechanisms underlying nitrite-induced cardioprotection are not known. We determined the ability of nitrite and nitrate to confer protection against myocardial infarction in two rat models of ischemia/reperfusion injury and the role of xanthine oxidoreductase, NADPH oxidase, nitric oxide synthase and K(ATP) channels in mediating nitrite-induced cardioprotection. In vivo and in vitro rat models of myocardial ischemia/reperfusion injury were used to cause infarction. Hearts (n=6/group) were treated with nitrite or nitrate for 15 min prior to 30 min regional ischemia and 180 min reperfusion. Xanthine oxidoreductase activity was measured after 15 min aerobic perfusion and 30 min ischemia. Nitrite reduced myocardial necrosis and decline in ventricular function following ischemia/reperfusion in the intact and isolated rat heart in a dose- or concentration-dependent manner with an optimal dose of 4 mg/kg in vivo and concentration of 10 microM in vitro. Nitrate had no effect on protection. Reduction in infarction by nitrite was abolished by the inhibition of flavoprotein reductases and the molybdenum site of xanthine oxidoreductase and was associated with an increase in activity of xanthine dehydrogenase and xanthine oxidase during ischemia. Inhibition of nitric oxide synthase had no effect on nitrite-induced cardioprotection. Inhibition of NADPH oxidase and K(ATP) channels abolished nitrite-induced cardioprotection. Nitrite but not nitrate protects against infarction by a mechanism involving xanthine oxidoreductase, NADPH oxidase and K(ATP) channels.     

NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent and -independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction

OBJECTIVE: We investigated the effect of apocynin, an NADPH oxidase inhibitor, in the impairment of vascular responses in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetic rat model) with or without (w/wo) N-nitro-l-arginine methyl ester treatment. METHODS: Male OLETF and littermate Long-Evans Tokushima Otsuka (LETO) (28 weeks old) rats were separated as follows: LETO w/wo apocynin (Gp C, Gp C-apo), OLETF w/wo apocynin (Gp DM, Gp DM-apo) and OLETF plus l-nitro arginine acetate ester w/wo apocynin (Gp DMLN, Gp DMLN-apo). Five days after, peritoneal macrophages were stimulated with thioglycolate. Two days after, they were evaluated. RESULTS: Plasma glucose and lipid levels remained unchanged. Acetylcholine-induced nitric oxide-dependent (NO-dependent) relaxation and nitroglycerin-induced NO-independent relaxation were improved in the Gp DMLN-apo, compared with that in Gp DMLN. Tone-related basal NO release and plasma NO(2) (-) and NO(3) (-) tended to be lower in Gp DM and Gp DMLN groups. The increased amount of superoxide anion released from macrophages in Gp DM and Gp DMLN was restored by apocynin. Intimal thickening was observed in aortae of Gp DM and Gp DMLN animals; however, there was little in aortae of Gp DM-apo and Gp DMLN(-) apo rats. Increased tumour necrosis factor-alpha (TNF-alpha) in the Gp DM and Gp DMLN was also restored by apocynin treatment. CONCLUSION: Apocynin restores the impairment of endothelial and non-endothelial function in diabetic angiopathy in OLETF without changing plasma glucose and lipid levels. NO and O(2) (-) may play a role in this process by decreasing TNF-alpha levels.     

还原型辅酶Ⅱ氧化酶抑制剂对慢性间歇缺氧大鼠血压的影响及相关机制

目的 探讨还原型辅酶Ⅱ(NADPH)氧化酶抑制剂罗布麻宁对慢性间歇缺氧(CIH)模型大鼠血压可能的影响及相关作用机制.方法 使用随机数字表法将30只雄性SD大鼠分为健康对照组、CIH组及罗布麻宁治疗组,每组10只.采用气囊加压法测定大鼠尾动脉收缩压,应用实时PCR检测外周血单核细胞NADPH氧化酶亚基p22phox的mRNA表达,并用Western blot检测胸主动脉组织匀浆中p22phox蛋白的表达,采用比色法测定胸主动脉组织匀浆中一氧化氮及超氧阴离子含量,采用化学比色法测定大鼠外周血丙二醛及超氧化物歧化酶(SOD)水平.各组均数之间比较采用单因素方差分析,组内两两比较采用SNK-q检验.结果 CIH组p22phox mRNA(2.85±0.47)及其蛋白(0.63±0.15)的表达明显高于健康对照组(2.26±0.48,0.27 ±0.13,q值分别为3.202、6.522,均P＜0.05),罗布麻宁治疗组p22phox mRNA(2.75±0.50)及其蛋白(0.57±0.16)的表达与CIH组比较两组无明显差异,但治疗后可显著逆转由慢性间歇缺氧导致的丙二醛、超氧阴离子及尾动脉收缩压的升高以及SOD和一氧化氮水平的降低.结论 NADPH氧化酶亚基p22phox的过度表达在慢性间歇缺氧导致的高血压发生过程中起重要作用,这可能是OSAHS患者并发高血压的病理生理基础之一;抑制NADPH氧化酶的活性可能对OSAHS合并高血压的治疗有一定积极的意义.     

Differential gene expression of NADPH oxidase (p22phox) and hemoxygenase-1 in patients with Type 2 diabetes and microangiopathy.

AIMS: While the downstream effects of increased reactive oxygen species (ROS) in the pathogenesis of diabetes were well studied, only a few studies have explored the cellular sources of ROS. We examined whether protection against oxidative stress is altered in patients with diabetes and microangiopathy by examining changes in NADPH oxidase (p22(phox)) and hemoxygenase-1 (HO-1) levels. METHODS: NADPH oxidase (p22(phox)) and HO-1 gene expression were probed by RT-PCR using leucocytes from patients with Type 2 diabetes without (n = 19) and with microangiopathy (n = 20) and non-diabetic subjects (n = 17). Levels of lipid peroxidation as measured by thiobarbituric reactive substances (TBARS) and protein carbonyl content (PCO) were determined by fluorimetric and spectrophotometric methods, respectively. RESULTS: p22(phox) gene expression (mean +/- SE) was significantly (P < 0.05) higher in diabetic patients with (0.99 +/- 0.04) and without microangiopathy (0.86 +/- 0.05) compared with control subjects (0.66 +/- 0.05). Consistent with the mRNA data, the p22(phox) protein expression and NADPH oxidase activity was also increased in cells from diabetic patients compared with control subjects. However, HO-1 gene expression was significantly (P < 0.05) lower in patients with (0.73 +/- 0.03) and without microangiopathy (0.85 +/- 0.02) compared with control subjects (1.06 +/- 0.03). The mean (+/- SE) levels of TBARS were significantly (P < 0.05) higher in diabetic patients with (14.36 +/- 1.3 nM/ml) and without microangiopathy (12.20 +/- 1.3 nM/ml) compared with control subjects (8.58 +/- 0.7 nM/ml). The protein carbonyl content was also significantly (P < 0.05) higher in diabetic patients with (1.02 +/- 0.04 nmol/mg protein) and without microangiopathy (0.84 +/- 0.06 nmol/mg protein) compared with control subjects (0.48 +/- 0.02 nmol/mg protein). In diabetic subjects, increased p22(phox) gene expression was negatively correlated with HO-1 and positively correlated with TBARS, PCO, HbA(1c) and diabetes duration. In contrast, HO-1 gene expression was correlated negatively with p22phox, TBARS, PCO, HbA(1c) and diabetes duration. CONCLUSION: Our results indicate that increased oxidative damage is seen in Asian Indians with Type 2 diabetes and microangiopathy and is associated with increased NADPH oxidase (p22(phox)) and decreased HO-1 gene expression.     

Setanaxib,a first-in-class selective NADPH oxidase 1/4 inhibitor for primary biliary cholangitis: A randomized,placebo-controlled,phase 2 trial

Background

Primary biliary cholangitis (PBC) is a rare liver disease with significant unmet need for second-line/add-on treatments. Setanaxib, a NOX1/4 inhibitor, has shown anti-fibrotic effects in in vitro and animal studies. This phase 2, randomized, multicentre study investigated the efficacy and safety of setanaxib in patients with PBC.

Methods

Patients with ≥6 months of ursodeoxycholic acid (UDCA) treatment were randomized 1:1:1 to oral setanaxib 400 mg once daily (OD), twice daily (BID), or placebo, in addition to UDCA for 24 weeks. Other inclusion criteria included alkaline phosphatase (ALP) ≥1.5 × ULN and gamma-glutamyl transferase (GGT) ≥1.5 × ULN. The primary endpoint was percentage change from baseline in GGT at Week 24; secondary endpoints included change from baseline in ALP, liver stiffness (LS; via transient elastography), fatigue at Week 24, and safety outcomes. p values compare setanaxib 400 mg BID and placebo groups.

Results

Of patients randomized (setanaxib 400 mg OD and BID: 38, and 36; placebo: 37), 104/111 completed Week 24. Mean (standard deviation [SD]) change in GGT to Week 24 was −4.9% (59.6%) for setanaxib 400 mg OD, −19.0% (28.9%) for setanaxib 400 mg BID, and −8.4% (21.5%) for placebo; p = .31. Patients treated with setanaxib 400 mg OD and BID showed decreased serum ALP levels from baseline to Week 24 (p = .002: setanaxib BID versus placebo). Patients treated with setanaxib 400 mg OD and BID showed mean (SD) percentage increases in LS to Week 24 of 3.3% (35.0%) and 7.9% (43.7%), versus 10.1% (33.1%) for placebo (p = .65). Changes in mean (SD) PBC-40 fatigue domain scores to Week 24 were +0.3% (24.9%) for setanaxib 400 mg OD, −9.9% (19.8%) for setanaxib 400 mg BID and +2.4% (23.1%) for placebo, p = .027. Two patients (one placebo, one setanaxib 400 mg BID) experienced serious treatment-emergent adverse events, deemed unrelated to study drug.

Conclusions

The primary endpoint was not met. However, the secondary endpoints provide preliminary evidence for potential anti-cholestatic and anti-fibrotic effects in PBC, supporting the further evaluation of setanaxib in a future phase 2b/3 trial.     

Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch

Aims/hypothesis Obesity is an independent risk factor for heart diseases but the underlying mechanism is not clear. This study examined cardiac contraction, oxidative stress, oxidative modification of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) and the myosin heavy chain (MHC) isoform switch in obese mice.Methods Mechanical properties were evaluated in ventricular myocytes from C57BL/6J lean and Lep/Lep obese mice (formerly known as ob/ob mice), including peak shortening (PS), time to 50 or 90% PS, time to 50 or 90% relengthening (TR₅₀, TR₉₀), maximal velocity of shortening/relengthening (±dL/dt), intracellular Ca²⁺ and its decay (τ). Oxidative stress, lipid peroxidation, protein damage and SERCA activity were assessed by glutathione/glutathione disulfide, malondialdehyde, protein carbonyl and ⁴⁵Ca²⁺ uptake, respectively. NADPH oxidase was determined by immunoblotting.Results Myocytes from Lep/Lep mice displayed depressed PS and ± dL/dt, prolonged TR₅₀, TR₉₀, elevated resting [Ca²⁺]_i, prolonged τ, reduced contractile capacity at high stimulus frequencies and diminished responsiveness to extracellular Ca²⁺ compared with lean controls. Cardiac glutathione/glutathione disulfide was decreased whereas malondialdehyde, protein carbonyl, membrane p47^phox and membrane gp91^phox were increased in the Lep/Lep group. SERCA isoenzyme 2a was markedly modified by oxidation in Lep/Lep hearts and associated with decreased ⁴⁵Ca²⁺ uptake. The MHC isozyme displayed a shift from the α to the β isoform in Lep/Lep hearts. Short-term incubation of angiotensin II with myocytes mimicked the mechanical defects, SERCA oxidation and ⁴⁵Ca²⁺ uptake seen in Lep/Lep myocytes. Incubation of the NADPH oxidase inhibitor apocynin with Lep/Lep myocytes alleviated contractile defects without reversing SERCA oxidation or activity.Conclusions/interpretation These data indicate that obesity-related cardiac defects may be related to NADPH oxidase activation, oxidative damage to SERCA and the MHC isozyme switch.     

NAD（P）H氧化酶P^22phox亚单位基因启动子区多态性与高血压病的关系

目的　探讨NAD(P)H氧化酶P2 2phox亚单位基因启动子区 - 930A/G多态性与原发性高血压及血脂水平的关系。方法　应用多聚酶链反应 -限制性片段长度多态性检测 12 3例高血压患者和 10 5例健康者P2 2 phox- 930A/G基因多态性。结果　高血压病组GG基因型频率为 0 .37,G等位基因频率为 0 6 0 ,明显高于正常对照组的 0 11和 0 36 (基因型频率比较 χ2 =2 5 17,P <0 0 1;等位基因频率比较 χ2 =2 6 2 1,P <0 0 1)。结论　P2 2phox- 930A/G基因多态性与高血压病有明显相关性 ,G等位基因是高血压病的危险因素