黄豆苷元对自发性高血压大鼠肾损害的保护作用

目的 探讨黄豆苷元对自发性高血压大鼠(SHR)肾损害的保护作用及其机制.方法 将符合条件的24只SHR随机分为黄豆苷元组(Dai组)、咪达普利组(Imi组)和生理盐水对照组(NS组),同时以8只同龄Wistar-Kyoto(WKY)大鼠作为正常对照组.前两组分别用黄豆苷元13.50 mg/(kg·d)和咪达普利0.90 mg/(kg·d)灌胃,NS组及正常对照组只给予等量的生理盐水.用药4周后用放射免疫法测定尿β2微球蛋白(β2-MG),颈动脉插管法测收缩压,分光光度法测定肾组织超氧化物歧化酶(SOD)和丙二醛(MDA).结果 与正常对照组比较,各组血压、尿β2-MG显著增多(P＜0.01),肾组织内的SOD活性降低.药物干预4周后与同期NS组比较,黄豆苷元明显降低尿β2-MG和MDA水平(P＜0.05),并能明显提高肾脏组织内的SOD活性;咪达普利则显著降低尿β2-MG和MDA水平(P＜0.05或P＜0.01),亦显著提高肾组织SOD活性(P＜0.01),但两组比较无统计学意义(P＞0.05).结论 黄豆苷元能明显改善高血压肾损害,其机制可能是通过清除自由基、抗脂质过氧化和保护内皮作用实现的,其作用与咪达普利相似.     

幼龄自发性高血压大鼠血管内皮功能研究

目的　本研究选取幼龄自发性高血压大鼠(SHR)作为研究对象 ,观察其尚未出现高血压时血浆一氧化氮 (NO)、血管壁一氧化氮合酶 (NOS)的情况及负荷运动对它的影响 ,从而进一步了解内皮功能在遗传性高血压发病中的地位。方法　 5～ 6wSHR、WKY各 2 8只随机分为静态组、运动组 ,静态组行有创血压测定、血浆NO及血管壁NOS测定 ,运动组行游泳负荷运动后行上述指标测定 ,分别比较静态组WKY、SHR 6min内的平均血压、峰血压、达峰时间、血浆NO的均数和运动组WHY、SHR的上述指标的均数 ,比较各组NOS免疫组化染色。结果　 (1)静态组WKY、SHR6min内的平均血压、峰血压、达峰时间有显著差异 (P <0 0 5 ) ;运动组WKY、SHR的平均血压、峰血压、达峰时间没有显著差异 (P >0 .0 5 ) ;(2 )静态组WKY、SHR的血浆NO无显著差异 (P <0 .0 5 ) ,运动组WKY、SHR的NO有显著差异(P <0 .0 5 ) ;无论是SHR还是SKY ,其运动组血浆NO均高于静态组 ,但WKY鼠运动组比静态组增高更明显 ;(3)各组血管壁NOS免疫组化染色范围未见明显不同。结论　SHR在高血压期前已存在内皮舒血管储备功能的不足。推测内皮舒血管功能的障碍可能参与了遗传性高血压的发病。     

一氧化氮合酶在自发性高血压大鼠中的表达

一氧化氮（NO）作为一种内源性活性物质和一类新的神经递质在20世纪80年代末期引起了广泛注意,而一氧化氮合酶（NOS）作为合成NO的关键酶在心脑血管疾病的发生、发展中起着重要作用。文章就NOS及其亚型在自发性高血压大鼠心血管、神经、肾脏等组织中的表达及其意义进行了综述。     

卡维地洛对高血压大鼠心肌成纤维细胞一氧化氮合酶-一氧化氮系统的影响

观察基础和卡维地洛干预条件下,自发性高血压大鼠和Wistar大鼠心肌成纤维细胞一氧化氮合酶-一氧化氤系统活性的变化。胰酶消化法分离、培养大鼠心肌成纤维细胞,采用硝酸还原酶法和分光光度法观察基础和卡维地洛干预条件下,培养基中一氧化氮合酶活性及一氧化氮含量的变化。结果发现,在基础状态下72 h,高血压大鼠组心肌成纤维细胞一氧化氮含量(66.6±3 5/μmol/L)及一氧化氮合酶活性(16.7±0.7 kU/L)较Wistar大鼠组(80.8±6.2/μmol/L和29.1±2.1 kU/L)显著降低,并有统计学意义(P<0.01);一氧化氮含量及一氧化氮合酶活性随卡维地洛浓度的增高而增加,均呈别量依赖性;另外,在不同浓度卡维地洛作用下,高血压大鼠组心肌成纤维细胞的一氧化氮含量随一氧化氮合酶活性的增强而增高,二者呈显著正相关(r=0.911,P<0.01)。结果提示,高血压大鼠心肌成纤维细胞的一氧化氮合酶一氧化氮系统功能异常,表现为一氧化氮合酶活性降低,一氧化氮含量减少。卡维地洛使心肌成纤维细胞内一氧化氯合酶一氧化氮系统活性显著增高,并呈浓度依赖性,其中对高血压大鼠的影响远远高于正常血压组,这可能是卡维地洛抑制血压增高的重要机制之一。     

通心络对自发性高血压大鼠血管内皮功能的影响

目的 观察通心络胶囊对自发性高血压大鼠(SHR)血管内皮功能的保护作用.方法 将24只SHR随机分为通心络组(TXL组)、咪达普利组(MD组)和生理盐水组(SHR组),每组8只.同时还有8只同龄Wistar-Kyoto(WKY)大鼠作为正常对照组.TXL组和MD组分别以通心络胶囊280 mg/(kg·d)和咪达普利0.90 mg/(kg·d)配成2 mL水溶液灌胃4周.SHR组与WKY组灌胃等量生理盐水.实验结束后取血测定内皮素-1(ET-1)、一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性.结果 SHR组NO浓度与SOD活性均低于WKY组(P<0.01),TXL组NO浓度与SOD活性则高于SHR组(P<0.01),SHR组ET-1、AngⅡ及MDA水平高于WKY组(P<0.01),TXL组ET-1、AngⅡ及MDA水平均低于SHR组,与MD组比较则无统计学意义(P>0.05).结论 通心络胶囊可能通过增加NO浓度和SOD活性,降低ET-1、AngⅡ及MDA水平,对血管内皮具有保护作用.     

2型糖尿病合并高血压患者血清NO、NOS水平的研究

目的　通过对 2型糖尿病 (2 - DM)合并高血压 (EH)患者血清一氧化氮 (NO)、一氧化氮合酶 (NOS)的测定 ,探讨其在 2 - DM合并 EH发生发展中的意义。方法　设正常对照组、单纯 2 - DM组和 2 - DM合并 EH组 ,分别测定血糖、胰岛素、血脂、NO及 NOS。结果　 2 - DM合并 EH组空腹胰岛素 (FINS)、舒张压 (DBP)和收缩压 (SBP)等均显著高于单纯 2 - DM组和正常对照组 ;胰岛素敏感指数 (ISI)和 NO均显著低于其他两组。相关分析显示 NO与 FINS和血压呈明显负相关 ,与 ISI呈显著正相关。结论　血清中 NO含量与胰岛素抵抗和血压密切相关 ,2 - DM患者血清 NO水平的降低可能参与了 2 - DM患者合并 EH的发病。     

一氧化氮合酶在自发性高血压大鼠中的表达

一氧化氮 (NO)作为一种内源性活性物质和一类新的神经递质在 2 0世纪 80年代末期引起了广泛注意 ,而一氧化氮合酶 (NOS)作为合成NO的关键酶在心脑血管疾病的发生、发展中起着重要作用。文章就NOS及其亚型在自发性高血压大鼠心血管、神经、肾脏等组织中的表达及其意义进行了综述。     

辛伐他汀对SHR心肌组织SOD、MDA、NOS、NO及心肌间质胶原含量的影响

目的观察辛伐他汀对自发性高血压大鼠(SHR)心肌纤维化的影响.方法 20只16周龄雄性SHR大鼠,随机分成2组(1)辛伐他汀组(n=10辛伐他汀2 mg/kg*d);(2)SHR空白对照组(n=10);(3)同龄雄性正常血压WKY大鼠对照组(n=10).给药12周后称量大鼠左室重量并计算大鼠左室重量指数;测定心肌组织丙二醛、超氧歧化酶、一氧化氮及一氧化氮合酶;用改良VG染色法使胶原特殊染色,计算机图像分析测量心肌间质及心肌小动脉周围胶原的胶原容积分数对心肌纤维化程度进行比较.结果辛伐他汀组与SHR组相比心肌超氧歧化酶无明显改变、丙二醛明显减少而心肌一氧化氮及结构型一氧化氮合酶(cNOS)活性明显升高;辛伐他汀组均未能有效降低SHR血压和左心室肥厚(P<0.05)但能使心室内、外膜及心肌小动脉周围的胶原减少.结论一氧化氮/活性氧平衡失调可能是导致高血压心肌纤维化的又一个重要因素;辛伐他汀抗纤维化作用可能与其抗氧化作用及改善心肌cNOS活性密切相关.     

原发性高血压患者微量蛋白尿与早期肾损害

目的：探讨尿液微量蛋白与高血压病(EH)早期肾功能损害的关系。方法：用速率免疫散射比浊法测定了105例EH思考和32例正常对照市的尿液微量白蛋白(mAL)、白蛋白(ALB)、α1微球蛋白(α1—MG)、β2微球蛋白(β2—MG)。结果：EH患早期即有α1—MG水平的升高(P＜0．05)。结论：尿液α1—MG的测定有利于EH患肾功能损害的早期诊断、治疗。     

早期糖尿病大鼠肾脏诱生型一氧化氮合酶基因表达

目的观察４周糖尿病大鼠肾脏血流动力学变化和肾脏皮、髓质诱生型一氧化氮合酶（ｉＮＯＳ）基因表达情况。方法应用整体廓清试验和半定量逆转录聚合酶链反应（ＲＴＰＣＲ）。结果糖尿病大鼠肾血浆流量（ＲＰＦ４．５４±０．２４ｍｌ／ｍｉｎ／１００ｇｗｔ）、肾小球滤过率（ＧＦＲ１．１５±０．０４ｍｌ／ｍｉｎ／１００ｇｗｔ）显著高于正常（ＲＰＦ３．４４±０．５０，ＧＦＲ０．９４±０．０３）；肾脏皮、髓质ｉＮＯＳｍＲＮＡ水平（经ＧＡＰＤＨ校正）亦明显升高（皮质１．４９±０．０１比正常１．００±０．００８；髓质３．９０±０．０８比正常１．００±０．０９）。结论一氧化氮（ＮＯ）增加可能是糖尿病早期肾脏高灌注、高滤过的重要原因。高水平ＮＯ即可直接扩张肾血管，导致ＲＰＦ、ＧＦＲ升高；又可能通过升高肾间质压，抑制管球反馈参与肾小球高灌注、高滤过的形成     

Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed,salt-sensitive hypertensive rats

We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg. kg(-1). day(-1)), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129+/-4 mm Hg, versus LS-F rats, 115+/-3 mm Hg, P<0.05; or versus HS-C rats, 116+/-5 mm Hg, P<0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129+/-4 mm Hg, versus HS-FP rats, 113+/-3 mm Hg, P<0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.     

NO及NOS在低氧大鼠肺组织和主动脉中的差异性及其意义

目的观察低氧性肺动脉高压大鼠肺组织匀浆、主动脉匀浆及出肺血和入肺血中一氧化氮（NO）的含量、一氧化氮合酶（NOS）的活性。方法将24只雄性SD大鼠随机分成4组,即常氧2周组、常氧3周组、低氧2周组、低氧3周组。采用间断负压低氧法制备大鼠低氧性肺动脉高压模型;右心室导管法测定最高肺动脉压（PAP）;左颈总动脉插管测量左颈总动脉压代表动脉血压（Psa）;计算右心室肥厚指数[RV/（LV+S）];采用硝酸还原酶法测定各组大鼠出、入肺血及肺组织和主动脉匀浆中的NO含量;用化学比色法测定各组大鼠肺组织和主动脉匀浆中NOS的活性;应用免疫组化染色法观察各组大鼠肺组织及主动脉eNOS在蛋白质水平表达的变化。结果低氧组大鼠的PAP[（43.4±4.4）mmHg,（51.8±4.2）mmHg,1mmHg=0.133kPa],RV/（LV+S）（32.3±1.0,37.0±1.6）均高于其正常对照组[（20.8±2.4）mmHg,（21.8±3.9）mmHg;21.3±1.0,20.3±1.2,P<0.01)],且随缺氧时间延长而增高（P<0.01）,而Psa与常氧对照组比无差别。低氧组大鼠的出、入肺血及肺组织匀浆中的NO含量、NOS活性及肺组织eNOS的表达量均较其常氧对照组显著降低（P<0.01）,出肺血与入肺血的NO含量无差别;主动脉匀浆中NO含量和NOS的活性及大鼠主动脉的eNOS染色在各组间未见明显差异。结论低氧时,大鼠肺组织中NO的含量及NOS的活性均较常氧时降低,而主动脉中二者的表达在低氧和常氧时却没有差异,这种差异性可能是低氧时引起肺动脉高压却很少导致高血压的机制之一。     

Increased vascular endothelin-1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats

The present study aimed to investigate whether altered expression levels of endothelin-1 (ET-1) and nitric oxide synthase (NOS) are related to the development of insulin-resistant hypertension. Male Sprague-Dawley rats were fed a fructose-rich diet for 5 weeks. Systolic blood pressure significantly increased in fructose-fed rats. While serum free fatty acid (FFA) and plasma nitrite/nitrate (NOx) levels did not significantly differ between the fructose-fed and control groups, plasma insulin and serum triglyceride (TG) concentrations significantly increased in the former. ET-1 mRNA expression in the aorta increased to 195% in fructose-fed rats. Neither the protein expression of constitutive NOS (cNOS) nor that of inducible NOS (iNOS) were significantly affected by fructose feeding. However, NOx levels in the aorta were significantly increased. These results indicate that an increased expression of vascular ET-1 may be causally related to the development of hypertension in fructose-fed rats. However, an altered role of the vascular nitric oxide (NO) pathway may not be primarily involved in the development of fructose-induced hypertension.     

大鼠同种异位心脏移植术后血清NO及心肌组织NOS活性的观察

目的　研究内源性一氧化氮（ＮＯ）与心脏移植急性排斥反应的关系。方法　本研究以大鼠同种异位心脏移植为研究对象，观察了术后３、５、７ 天的血清ＮＯ 水平以及心肌组织一氧化氮合成酶（ＮＯＳ）的活性。结果　在急性排斥反应发生的早期开始血清ＮＯ 水平就已显著升高（术后３、５、７ 天皆为Ｐ ＜ ０．０１）；心肌组织ＮＯＳ活性亦显著高于对照组（术后３ 天Ｐ ＜ ０．０５，术后５ 天Ｐ＜ ０．０１，术后７ 天Ｐ ＜ ０．０５）。结论　血清ＮＯ 水平的检测对于心脏移植急性排斥反应的发生可能具有早期的辅助诊断意义。     

Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats.

OBJECTIVES: We sought to examine the hypothesis that a pharmacologic up-regulation of endothelial nitric oxide synthase (eNOS) combined with a reversal of eNOS uncoupling provides a protective effect against cardiovascular disease. BACKGROUND: Many cardiovascular diseases are associated with oxidant stress involving protein kinase C (PKC) and uncoupling of eNOS. METHODS: Messenger ribonucleic acid (mRNA) expression was analyzed with RNase protection assay or quantitative real-time polymerase chain reaction, vascular nitric oxide (NO) with spin trapping, and reactive oxygen species (ROS) with dihydroethidium fluorescence. RESULTS: Aortas of spontaneously hypertensive rats (SHR) showed an elevated production of ROS when compared with aortas of Wistar-Kyoto rats (WKY). The aortic expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox1, Nox2, Nox4, and p22phox) was higher in SHR compared with WKY. In SHR, aortic production of ROS was reduced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), indicating eNOS "uncoupling" in hypertension. Oral treatment with the PKC inhibitor midostaurin reduced aortic Nox1 expression, diminished ROS production, and reversed eNOS uncoupling in SHR. Aortic levels of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) were significantly reduced in SHR compared with WKY. Midostaurin normalized BH4 levels in SHR. In both WKY and SHR, midostaurin increased aortic expression of eNOS mRNA and protein, stimulated bioactive NO production, and enhanced relaxation of the aorta to acetylcholine. Midostaurin lowered blood pressure in SHR and, to a lesser extent, in WKY; the compound did not change blood pressure in WKY made hypertensive with L-NAME. CONCLUSIONS: Pharmacologic interventions that combine eNOS up-regulation and reversal of eNOS uncoupling can markedly increase bioactive NO in the vasculature and produce beneficial hemodynamic effects such as a reduction of blood pressure.     

Endothelial nitric oxide synthase protein is reduced in the renal medulla of two-kidney, one-clip hypertensive rats

OBJECTIVE : We studied endothelial nitric oxide synthase (eNOS) expression in the kidneys of two-kidney, one-clip renal hypertensive rats (2K1C) before and after removal of the clip (unclipping, UC). We hypothesised that the haemodynamic changes induced by 2K1C and UC would change eNOS expression in the two kidneys. METHODS : Six weeks after inducing 2K1C, mean arterial pressure (MAP) was measured in conscious rats and hypertension reversed by UC. Left and right kidney eNOS protein in cortex and outer medulla was semi-quantified using immunoblotting. Groups were; normotensive (n = 10), 2K1C (n = 10), 3 h (n = 10), 48 h (n = 7) and 4 weeks (n = 7) after UC. The effect of 7 days of aldosterone or angiotensin II (Ang II) infusion on medullary eNOS protein was tested as well as the effect of L-NAME (nitric oxide (NO) synthase inhibitor) on medullary blood flow (MBF) in anaesthetized 2K1C. RESULTS : UC reduced MAP from 178 +/- 5 to 134 +/- 3 mmHg after 3 h and normalized MAP at 48 h and 4 weeks. The medulla from 2K1C kidneys contained about 33% less eNOS protein compared with normotensive kidneys (P < 0.05). This difference was still evident at 3 h (P < 0.05), but completely reversed at 48 h and 4 weeks after UC. Similar levels of eNOS expression were seen in the left and right kidney at all time points. Cortical eNOS was increased in kidneys from 2K1C. Neither Ang II nor aldosterone affected eNOS expression in the medulla. MBF was under similar influence of NO in 2K1C compared with normotensive kidneys. CONCLUSIONS : 2K1C is associated with reduced levels of eNOS protein in the renal medulla of both clipped and contralateral kidney. eNOS expression in right and left kidney was not changed despite expected large changes in haemodynamics of the two kidneys. The reduced level of eNOS may be associated with a reduction in MBF and thus be of patho-physiological importance in renovascular hypertension.     

衰老对大鼠阴茎组织神经型一氧化氮合成酶的影响

目的　探讨老年性阳萎的发病机制。　方法　取不同月龄雄性Ｗｉｓｔａｒ大鼠阴茎海绵体组织，行特异性抗神经型一氧化氮合成酶（ｎＮＯＳ）免疫组化染色，计数ｎＮＯＳ神经纤维含量。　结果　１９～２１ 月龄组大鼠阴茎中阳性染色纤维数为（５０．８３±４．２２）条，明显少于５ 月龄组的（１２８．８８±３６．７８）条和１０ 月龄组的（１０６．２５±１２．０６）条，差异均有显著性（Ｐ＜ ０．０１），而１０ 月龄组与５月龄组差异无显著性（Ｐ＞ ０．０５）。　结论　衰老可造成大鼠阴茎中ｎＮＯＳ的减少，可能与老年性阳萎的发病有关