非酒精性脂肪性肝炎的ACE-ID与AT1R-A1166C多态性研究

目的:研究血管紧张素转化酶(ACE)基因ID多态性和血管紧张素Ⅱ1型受体(AT1R)基因A1166C多态性与日本高知地区非酒精性脂肪性肝炎(NASH)易感性的相关性,从基因学角度探讨NASH的发生发展机制,为NASH的预防、诊断和治疗提供一定的理论依据。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-PFLP)方法对日本高知地区104例NASH患者和150例正常人ACE-ID基因和AT1R-A1166C基因多态性进行分析。结果:NASH病例组D等位基因频率显著高于正常对照组(P0.01);NASH病例组的DD基因型频率显著高于正常对照组(P0.01);NASH病例组A等位基因频率与正常对照组相比差异无显著(P(0.05)。NASH病例组AA基因型频率与正常对照组相比差异无显著(P(0.05)。结论:ACE-ID基因位于内含子16上D等位基因与DD基因型与NASH的发生发展显著相关,可能是促进NASH发生的原因之一;AT1R-A1166C基因多态性与NASH的发生发展尚未显示相关性。     

肾素-血管紧张素系统基因多态分析在壮族IgA肾病预后判断中的价值

目的:通过分析肾素-血管紧张素系统(RAS)3个关键基因血管紧张素Ⅱ1型受体(AT1R)基因A1166C多态、血管紧张素Ⅰ转化酶(ACE)基因插入/缺失(I/D)多态和血管紧张素原(AGT)基因M235T多态在壮族IgA肾病患者中的分布,进而探讨RAS基因多态在壮族IgA肾病预后判断中的价值.方法:选取壮族IgA肾病患者68例(肾病组),并选取70例健康体检者作为健康对照组.采用直接聚合酶链反应和聚合酶链反应-限制性片段长度多态性技术检测RAS ACE基因I/D多态、AT1R基因A1166C多态和AGT基因M235T多态,并分析其与肾脏病变程度、蛋白尿、高血压、肾功能损害等的关系.结果:肾病组ACE基因I/D多态性与健康对照组比较差异有统计学意义,DD基因型和D等位基因在肾病组中占显著优势(P＜0.05),而不同HAAS病理分级比较,ACE I/D多态DD基因型在≥Ⅲ级组中占显著优势(P＜0.05),肾损害组DD基因型分布频率高于无肾损害组(P＜0.05),ACE基因I/D多态在伴蛋白尿组和不伴蛋白尿组、伴高血压组和不伴高血压组中的分布差异均无统计学意义;各组中AT1R A1166C和AGT M235T基因型与等位基因分布频率差异均无统计学意义.结论:ACE I/D多态的DD基因和D等位基因是壮族IgA肾病发生的易感因素之一,携带DD基因患者易于表现为严重病理分级和出现肾功能损害,DD基因型是预测壮族IgA肾病预后不良的标志.     

血管紧张素系统基因多态性与原发性高血压的相关研究

目的：探讨中国人血管紧张素原（angiotensinogen,AGT)基因的蛋白产物M235T、血管紧张素Ⅱ-I型受体（AT1R)基因的蛋白产物A1166C以及血管紧线素转换酶（angiotensin convertingenzyme,ACE)基因I／D多态性与高血压病（hypertension,HT)的关系。方法：用PCR以及PCR加酶解方法检测了161例HT患者及134名健康人（normotensive controls,NT)ACEI/D基因多态性、AGTM235T及AT1RA1166C突变,并检测了血清ACE活性。结果：HT组ACEI／D基因多态性等位基因频率I为0．571,D为0．429,等位基因频率及基因型频率与NT组比较差异无显著性（P＞0．05）;＜60岁HT组D等位基因频率（0．457)显著高于NT组（0．358,P＜0．05）。HT组与NT组的AGT235T分别为0．813及0．832,两组间差异无显著性。AT1RA1166C的C等位基因频率HT组为0．021,NT组为0．053,两组间差异无显著性;但在＜60岁NT组AGTM235T显著高于NT组。两组中均发现ACE基因型与血清ACE活性相关。HT组DD－TT及ID－TT联合基因型显著高于对照组。结论：D等位基因及AGT235T对于HT早期发病可能有重要意义,DD－TT及ID－TT基因型人群可能是高血压发病的高危人群。     

ACE和AT1R基因多态性与原发性高血压易感性及与替米沙坦降压疗效的关系

目的 研究ACE基因和AT1R基因A1166C多态性与湖南地区汉族原发性高血压（PH）的关系及与替米沙坦的降压疗效关系.方法 利用聚合酶链反应-限制性片断长度多态性（PCR-RFLJ））对湖南地区汉族285例健康对照者（CON组）和246例原发性高血压（PH）患者（PH组）ACE插入和（或）缺失（I/D）突变和AT1R A1166C等位基因突变进行检测,分析两组问基因型和等位基因的频率分布.给予PH组中替米沙坦治疗12周,观察服药前后的疗效.采用Logistic多元回归分析基因多态性与PH的相关性.结果 PH组ACE基因型分布为DD 25.2%（62/246）、ID 27.6%（68/246）、II47.2%（116/246）;AT1R基因型分布为从61.4%（151/246）、AC 31.3%（77/246）、CC 7.3%（18/246）,其中ID和AC基因型与CON组差异有统计学意义（P〈0.05）;D、I等位基因频率与CON组差异无统计学意义（P〉0.05）;A、C与CON组差异有统计学意义（P〈0.05）.替米沙坦治疗12周后,ACE基因DD型与ID型降压疗效显著优于II型,收缩压分别下降（26.31±9.16）mm Hg、（22.92±10.21）mm Hg和（15.67±8.94）mm Hg,mm Hg=0.133 kPa,P〈0.05.AT1R基因AA型降压疗效优于AC＋CC基因型,收缩压分别下降（15.00±8.64）mm Hg和（10.37±8.04）mn Hg,舒张压分别下降（14136±6.01）mm Hg和（8.83±5.93）mm Hg,均P〈0.05.AT1R基因AC基因型是PH的独立危险因素.结论 ACE和AT1R基因多态性与湖南地区汉族人PH具有一定关系.携带ACE D和AT1R1622A等位基因的PH患者对替米沙坦的降压反应较好.     

血管紧张素Ⅱ-1型受体基因多态性与冠心病的关系

目的探讨深圳地区冠心病(CAD)与血管紧张素Ⅱ的1型受体(AT1R)基因A1166C多态性的关系.方法分别采用PCR及PCR-AfⅡ酶切法,检测102例CAD患者和148例健康对照的ACE和AT1R基因型.结果CAD组与对照组AT1R基因型频率分布无显著性差异(P＞0.05).结论深圳地区CAD的发生与AT1R基因A1166C多态性无关.     

ACE和AT1R基因多态性与原发性高血压易感性及与替米沙坦降压疗效的关系

目的 研究ACE基因和AT1R基因A1166C多态性与湖南地区汉族原发性高血压(PH)的关系及与替米沙坦的降压疗效关系.方法 利用聚合酶链反应-限制性片断长度多态性(PCR-RFLJ))对湖南地区汉族285例健康对照者(CON组)和246例原发性高血压(PH)患者(PH组)ACE插入和(或)缺失(I/D)突变和AT1R A1166C等位基因突变进行检测,分析两组问基因型和等位基因的频率分布.给予PH组中替米沙坦治疗12周,观察服药前后的疗效.采用Logistic多元回归分析基因多态性与PH的相关性.结果 PH组ACE基因型分布为DD 25.2%(62/246)、ID 27.6%(68/246)、II47.2%(116/246);AT1R基因型分布为从61.4%(151/246)、AC 31.3%(77/246)、CC 7.3%(18/246),其中ID和AC基因型与CON组差异有统计学意义(P<0.05);D、I等位基因频率与CON组差异无统计学意义(P>0.05);A、C与CON组差异有统计学意义(P<0.05).替米沙坦治疗12周后,ACE基因DD型与ID型降压疗效显著优于II型,收缩压分别下降(26.31±9.16)mm Hg、(22.92±10.21)mm Hg和(15.67±8.94)mm Hg,mm Hg=0.133 kPa,P<0.05.AT1R基因AA型降压疗效优于AC+CC基因型,收缩压分别下降(15.00±8.64)mm Hg和(10.37±8.04)mn Hg,舒张压分别下降(14136±6.01)mm Hg和(8.83±5.93)mm Hg,均P<0.05.AT1R基因AC基因型是PH的独立危险因素.结论 ACE和AT1R基因多态性与湖南地区汉族人PH具有一定关系.携带ACE D和AT1R1622A等位基因的PH患者对替米沙坦的降压反应较好.     

血管紧张素系统基因多态性与支架内再狭窄的相关性研究

目的探讨肾素-血管紧张素系统(RAS)中血管紧张素原(AGT)、血管紧张素Ⅰ转换酶(ACE)和受体(AT1R)的基因多态性与PTCA加支架置入术后再狭窄(ISR)发生的相关性.方法 103例行PTCA加支架置入术的患者,分为狭窄组和未狭窄组,应用PCR-RFLP及AFLP方法对ACE和AT1R基因进行基因分型并分别计算基因型频率,卡方检验确定两组间差异的显著性.结果 ACE基因DD型患者比DI型、II型患者有较高的再狭窄发生率(χ2 =9.759,P=0.008);AT1R (A1166C)基因多态与ISR无明显相关性(χ2 =0.759,P=0.372).结论 RAS系统中ACE(DD)基因多态型可能是上海汉族冠心病人群PTCA后ISR发生的遗传指标,而D等位基因则可能是ISR的预测因子.     

血管紧张素Ⅱ-1型受体基因A1166C多态性与高血压的相关性研究初探

目的建立高血压的病例对照组,研究血管紧张素Ⅱ-1型受体（AT1R）基因A1166C多态性与国人高血压的关系,为高血压病的诊断、治疗及易患性研究提供依据。方法应用聚合酶链反应,限制性内切酶酶解的方法检测83例原发性高血压患者（高血压组）和64例健康人（对照组）的AT1R基因型,比较各组间的基因分布差异,分析AT1R基因A1166多态性与高血压的关系。结果高血压患者AT,R基因型AA、AC、CC的频率分别为57．8％、38．6％、3．6％与正常对照组的67．2％、29．7％、2．7％相比较,无显著性差异（P〉0．05）。结论高血压是“基因-基因”与“基因-环境”相互作用所致的多基因遗传性疾病,AT1R仅为肾素血管紧张素系统成员之一的基因受体,A1166C多态性位于3’端非翻译区内,其可能对AT1R的表达起调控作用;我们发现AT1R的C等位基因频率在高血压组的分布较正常组高,但无统计学意义,尚不能确定AT1R基因A1166C多态性与高血压有相关性。     

原发性高血压合并脑梗塞患者血管紧张素Ⅱ-1型受体基因多态性的研究

目的 探讨血管紧张素Ⅱ－1型受体（angiotensin Ⅱ type 1 receptor,AT1R)基因A1166／C多态性与原发性高血压及合并脑梗塞的关系。方法 应用聚合酶链反应－限制性片段长度多态性方法检测70名健康人、72例原发性高血压无合并症患者及70例原发性高血压合并脑梗塞患者的AT1R基因型；生化技术测定血脂水平。结果 原发性高血压无合并症组及合并脑梗塞组的C等位基因频率分别为11．1％和10．7％，均显著高于正常对照组的3．6％（P＜0．05）；而两者之间的C等位基因频率差异无显著性（P＞0．05）；牟发性高血压患者血浆脂蛋白a水平与AT1R基因正相关。结论 提示AT1R基因可能是原发性高血压的重要遗传因素，但与高血压病患者是否易患脑梗塞无关。     

血管紧张素原、血管紧张素Ⅱ一型受体基因多态性与原发性高血压的相关性研究

目的 :探讨血管紧张素原AGT(M2 3 5T)、血管紧张素Ⅱ一型受体AT1 R(A1166C)基因多态性与中国四川籍人群原发性高血压(EH)的关系。方法 :采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFLP)方法分析人类白细胞染色体DNA中AGT、AT1 R基因多态性。结果 :12 2例EH病例组与 87例正常对照组AGT等位基因频率T、M分别为 :T :0 .82 8vs 0 .661,M :0 .172vs 0 .3 3 9。AT1 R等位基因频率A、C分别为 :A :0 .968vs 0 .989,C :0 .0 3 2vs 0 .0 11。各基因型频率及等位基因频率符合Hardy Weinberg平衡定律。EH病例组AGT基因T等位基因频率和TT型明显高于对照组(χ2 =11.7,P <0 .0 1和 χ2 =15 .6,P <0 .0 1)。结论 :AGT基因多态性与EH密切相关 ;而AT1 R基因多态性与EH无关。     

Cross-tachyphylaxis of the pressor response to angiotensins in conscious rabbits

The effect of tachyphylasix to angiotensin II amide on the pressor potency of angiotensin I, II and III and noradrenaline was investigated in conscious rabbits with indwelling cannulae. No significant difference was observed between the reduction in responses to angiotensin II (58±4%) and angiotensin III (42 ±6%) but angiotensin I (15±5%) and noradrenaline (17±10%) responses were less markedly inhibited. If all angiotensin I pressor activity was mediated through its conversion to angiotensin II one would expect an equivalent degree of cross-tachyphylaxis to occur with the two peptides. Our results suggest that angiotensin I may have significant inherent pressor activity of its own, independent of conversion. This compound is already known to have activity at other target tissues. The absence of a significant difference in the degree of tachyphylaxis with angiotensin II and III may indicate they have substantially common pathways as pressor agents.     

Noradrenergic and opioidergic alterations in neuropathy in different rat strains

The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas delta-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance.     

Chronic intermittent hypoxia augments chemoreflex control of sympathetic activity: Role of the angiotensin II type 1 receptor

Chronic exposure to intermittent hypoxia (CIH) increases carotid sinus nerve activity in normoxia and in response to acute hypoxia. We hypothesized that CIH augments basal and chemoreflex-stimulated sympathetic outflow through an angiotensin receptor-dependent mechanism. Rats were exposed to CIH for 28 days: a subset was treated with losartan. Then, lumbar sympathetic activity was recorded under anesthesia during 20-s apneas, isocapnic hypoxia, and potassium cyanide. We measured carotid body superoxide production and expression of angiotensin II type-1 receptor, neuronal nitric oxide synthase, and NADPH oxidase. Sympathetic activity was higher in CIH vs. control rats at baseline, during apneas and isocapnic hypoxia, but not cyanide. Carotid body superoxide production and expression of angiotensin II type 1 receptor and gp91^phox subunit of NADPH oxidase were elevated in CIH rats, whereas expression of neuronal nitric oxide synthase was reduced. None of these differences were evident in animals treated with losartan. CIH-induced augmentation of chemoreflex sensitivity occurs, at least in part, via the renin–angiotensin system.     

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT₁ receptor (AT₁-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO₂ = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT₁-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT₁-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT₁-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT₁-R staining, but C animals showed weak iNOS and AT₁-R staining. Macrophages of L and P animals showed moderate and weak AT₂-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT₁-R blockade. We suggest that AT₁-R blockade might act through AT₂-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.     

Angiotensin II receptor subtype distribution in the rabbit brain

Previous work has reported that the distribution of AT(1) binding sites in the rabbit brain is similar to that in the rat, but AT(2) binding sites are confined to the septum and cerebellum of the rabbit brain. This receptor autoradiographic study was designed to enhance the detection of angiotensin II binding sites by using greater radioligand concentrations, and to survey the midbrain in more detail than in previous studies. Tissue sections from five rabbit forebrains, three midbrains, and three hindbrains were incubated with 520 pM (125)I-sar(1)ile(8) angiotensin II. The results confirm abundant AT(1) binding in regions involved in cardiovascular and drinking regulation: the nucleus of the solitary tract, ventrolateral medulla, subfornical organ, organum vasculosum of the lamina terminalis, median eminence, and several hypothalamic structures. Novel AT(1) binding sites were discovered in the pituitary, retrorubral field, periolivary region, dorsolateral nucleus of the lateral lemniscus, dorsal raphe, and laterodorsal tegmental nuclei. The distribution of AT(1) binding was similar to the distribution of monoaminergic neurons. AT(2) binding was moderately dense and well visualized in the cerebellum. In contrast to the rat, AT(2) binding was not detected in the inferior olive of the rabbit, but lobe 9 of the cerebellum exhibited a banding pattern of AT(2) binding reminiscent of the pattern of neuronal projections from the inferior olive. It is possible that AT(2) protein is observed at different stages of axonal transport between the inferior olive and the cerebellum in the two species. Our results did identify new AT(2) binding sites in the superior colliculus and cerebral cortex, but it is clear that AT(2) binding in the rabbit brain is weak and is not as widely distributed as in the rat.     

Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure

Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin–angiotensin–aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1–7 generation, is largely unknown. This issue is of a special interest since angiotensin 1–7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n = 9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n = 8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P < 0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P < 0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P < 0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P < 0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).     

血管紧张素在培养乳鼠心肌细胞肥大发生中的作用

本实验观察到血管紧张素Ⅰ、Ⅱ(AngⅠ、AngⅡ)均可促进培养的乳鼠心肌细胞(MC)DNA、RNA和蛋白质的合成。并发现随着AngⅠ和AngⅡ作用时间的延长,对MC的RNA和蛋白质合成的促进作用也逐渐增强,而对其DNA合成的促进作用则有一定的时间界限。此外,还发现在AngⅠ和AngⅡ长期作用下可使MC体积增大。当AngⅠ和血管紧张素转换酶(ACE)抑制剂同时加入培养基,则无上述结果发生。这提示血管紧张素可能在心肌肥大的发生中起一定作用,而且AngⅠ是通过MC本身的ACE将其转化为AngⅡ后才起作用的。     

Stimulation of proximal tubular sodium reabsorption by ile5 angiotensin II in the rat kidney

A direct dose-dependent stimulation or inhibition by val⁵-angiotensin II of sodium reabsorption in the rat proximal nephron has been shown using stationary microperfusion combined with perfusion of the peritubular capillaries. Since the circulating form of the hormone in the rat has been suggested to be the ile⁵-analogue these experiments have been repeated using the ile⁵-peptide at peritubular concentrations covering the normal physiological range (10^–10–10^–13M). Comparison of the results with the previously published data shows no significant difference between the actions of these two analogues. At the concentrations tested both caused significant stimulation of sodium reabsorption with a maximum effect at 10^–11M.     

Bestimmung der Plasmareninaktivität durch radioimmunologischen Nachweis von Angiotensin I

Zusammenfassung 1. Die radioimmunologische Bestimmung der Plasmareninaktivität, bei der das nach Inkubation von Plasma bei 37° freigesetzte Angiotensin I gemessen wird, erwies sich der biologischen Reninbestimmung als überlegen. Die von Haber beschriebene Methode wurde dahingehend modifiziert, daß die Inkubation des Plasmas nicht bei pH 7,4, sondern bei pH 5,5 durchgeführt wird, um eine optimale Hemmung der Amino- und Endopeptidasen des Plasmas zu erzielen. Mit dieser Methode können Plasmareninaktivitäten zwischen 0,1 und 1000 ng Angiotensin 1/ml Plasma erfaßt werden.2. Der Vergleich zwischen radioimmunologischer und biologischer Bestimmung der Plasmareninaktivität ergab, daß die radioimmunologisch bestimmten Werte um einen vom Ausgangswert abhängigen Faktor höher als die biologisch bestimmten lagen. Die Differenz zwischen den bolden Methoden ist durch einen wertabhängigen Verlust von freigesetztem Angiotensin I bei der Elution, die beim biologischen Verfahren nach Boucher erforderlich ist, sowie durch die geringere pressorische Wirkung von Angiotensin I gegenüber Angiotensin II bedingt, da bei der biologischen Methode die pressorische Wirkung des Eluats nicht gegen Angiotensin I, sondern gegen Angiotensin II bestimmt wird.     

缬沙坦的抗动脉粥样硬化作用及可能机制

目的: 探讨缬沙坦是否能抑制兔动脉粥样硬化的发展及其可能机制。方法: 24只日本大耳白兔随机分为3组(每组8只): (1)对照组: 普通饮食饲养16周; (2)胆固醇组: 含1.5%胆固醇饲料喂养16周; (3) 缬沙坦组: 含1.5%胆固醇饲料喂养16周,并于后4周饮水中给予缬沙坦3 mg·kg^-1·d^-1治疗。实验过程中监测血压、血脂变化。于16周末取主动脉观察斑块的分布、面积,并采用免疫组织化学方法检测斑块内主要组成细胞量的变化及活化核转录因子-κB的变化。结果: 胆固醇组及缬沙坦组的血脂水平显著高于对照组(P＜0.05),而前两者之间无明显差异。缬沙坦组主动脉斑块/内膜面积比较胆固醇组少30%,斑块中单核/巨噬细胞数量少20%,而平滑肌细胞数量却有所增加。此外,缬沙坦组核因子-κB的活化及其靶基因细胞间粘附分子-1的表达亦较胆固醇组显著减少。结论:缬沙坦可抑制兔动脉粥样硬化的发展,其机制可能与抑制了单核/巨噬细胞的增殖和/或聚集、抑制了核因子-κB的活化有关。