卡托普利对幼年大鼠自发性高血压形成与肾素系统的作用

作者观察单剂量及长期灌饲卡托普利对卒中易感型自发性高血压大鼠(stroke-prone sponta-neously hypertensive rat,SHRsp)的作用。发现它可抑制其高血压的自发形成,明显降低血清血管紧张素转化酶(serum angiotensin convertingenzyme,SACE)活性水平,减少血浆血管紧张素Ⅱ(angiotensinⅠ,AⅠ)浓度,反馈性增加血浆肾素活性(plasma tenin activity,PRA)。提示肾素血管紧张素系统(renin-angiotensin system,RAS)可能在这类大鼠的高血压发生和维持上起一定作用。     

白芍总苷对代谢综合征-高血压大鼠改善胰岛素敏感性、降压和抗氧化作用

目的：探讨白芍总苷（TGP）对代谢综合征-高血压（metabolic syndromic—hypertension,MS—Ht）大鼠血压的作用,检测胰岛素敏感性、细胞因子、血管活性物质以及氧化应激的改变,研究其作用机制。方法：采用高脂、高糖饮食喂饲SD大鼠,连续8周,当造模动物出现高血压、糖耐量减退,MS—Ht病理模型建立成功;然后将大鼠随机分为模型对照、二甲双胍（metformin,Met）200mg／kg和TGP150、50mg／kg两个剂量组;分别灌胃给药或蒸馏水,qd×4周,实验结束时,测定大鼠血压、空腹血糖（FBG）和口服糖耐量试验2h血糖（OGTT-2 hBG）、血浆胰岛素（Fins）,并计算胰岛素敏感性（ISI）和胰岛素抵抗指数（HOMA—IRI）;测定游离脂肪酸（FFA）、TNF—α、内皮素（ET-1）、肾素-血管紧张素（AngⅡ）、NO和丙二醛（MDA）含量以及一氧化氮合酶（NOS）和超氧化物歧化酶（SOD）活性。结果：与正常对照组比较,MS—Ht大鼠血压升高;FBG、OGTT-2hBG和Fins含量增高;ISI减弱、而HOMA—IRI增强;FFA、TNF—α、ET-1、肾素-AngⅡ和MDA含量增高（P〈0．05或P〈0．01）;NO含量和NOS及SOD活性降低（P〈0．05或P〈0．01）。Met和TGP150mg／kg增强ISI,而降低HO—MA—IRI,纠正高胰岛素血症（P〈0．05或P〈0．01）,降低FFA、TNF—α、ET-1、肾素-AngⅡ和MDA含量（P〈0．05或P〈0．01）,提高NO含量和NOS及SOD活性;而Met能降低FBG、OG—TT-2hBG含量（P〈0．05或P〈0．01）;与TGP150mg／kg组比较,差异无统计学意义（P〉0．05）;TGP50mg／kg组,除降低肾素、AngⅡ和FFA含量外（P〈0．05）,对其余指标,差异均无统计学意义（P〉0．05）。结论：TGP和Met能对抗MS—Ht大鼠胰岛素抵抗、增强胰岛素敏感性、纠正高胰岛素血症,拮抗ET-1、肾素-AngⅡ系统和氧化应激反应,提高NO和NOS功能,降低血压;TGP不具直接降血糖作用,与Met不同。TGP以上效应呈量效关系。     

卡托普利长期治疗自发性高血压大鼠对循环和局部肾素—血管紧…

目的：探讨卡托普利长期治疗自发性高血压大鼠（ＳＨＲ）对循环和局部肾素－血管紧张素系统的影响。 方法：ＳＧＲ♂鼠宫内期给卡托普利治疗（１００ｍｇ·ｋｇ＾－１·ｄ＾－１），到１６ｗｋ停药。分别在１６ｗｋ和４０ｗｋ处死。测定收缩压、左室重与体重比、左室心肌和血浆血管紧张素Ⅱ（ＡⅡ）浓度、主动脉和血清血管紧张素转换酶（ＡＣＥ）活性、肾脏和肝脏血管紧张素原基因表达、肾脏肾素基因表达。 结果：治疗显降低ＳＨ     

胰腺肾素-血管紧张素系统在胰岛素抵抗和代谢综合征中的作用及机制研究进展

目的：综述胰腺肾素．血管紧张素系统（RAs）在胰岛素抵抗和代谢综合征中的作用及机制。方法：查阅相关文献,总结RAS与胰岛素抵抗和代谢综合征发生的相关因素,如炎症、氧化应激、胰岛B细胞功能、脂联素等之间的关系,以及RAS阻滞引起的这些因素的变化。结果与结论：血管紧张素（Ang）Ⅱ产生可促进炎症发生、降低胰岛血流量、胰岛素分泌,降低脂联素并增加氧化应激,这些可能最终导致胰岛B细胞功能不全和胰岛素抵抗。血管紧张素转换酶抑制剂（ACE）或AngⅡ受体Ⅰ型（ATl．R）阻滞药可减弱AngⅡ对胰岛血流量、胰岛素分泌和氧化应激的影响。胰腺肾素．血管紧张素系统在胰岛素抵抗和代谢综合征中起着重要的作用,RAS阻滞改善葡萄糖稳态的机制可能是增加了胰岛素水平,改善了胰岛素抵抗。     

代谢综合征患者血清肾素-血管紧张素-醛固酮水平及临床意义

目的 探讨代谢综合征(metabolic syndrome,MS)患者血清肾素(REN)、血管紧张素(Ang)、醛固酮(ALD)的水平及其与临床检测指标的相关性.方法 选择2014年2月—2016年6月120例MS住院患者为MS组和120例正常体检者为对照组.对两组的血清REN、Ang、ALD、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(PBG2h)和体重指数(BMI)等进行检测并比较.结果 MS组血清REN、AngⅠ、AngⅡ、ALD、TG、TC、LDL-C、FPG、PBG2h、BMI水平以及高血压和高血糖明显高于对照组(P<0.01),而HDL-C低于对照组(P<0.01).MS患者血清AngⅡ与HDL-C负相关(r=-0.256,P=0.007),与TG、TC、BMI、FPG、PBG2h和高血压呈正相关(r=0.920、0.410、0.310、0.410、0.423和0.568,P均<0.01).结论 REN、Ang和ALD在MS组患者血清中水平较高,可能与MS的发生与发展有关.     

益肾I方对多囊卵巢综合征—代谢综合征大鼠拮抗胰岛素抵抗抑制氧化应激及调血脂作用

目的观察益肾I方对多囊卵巢综合征-代谢综合征(PCOS-MetS)大鼠胰岛素抵抗(IR)、血脂异常及氧化应激-自由基损伤的作用。方法采用十一酸睾酮加绒毛膜促性腺激素(HCG)建立PCOS-MetS大鼠模型,连续口服给予二甲双胍或不同剂量的益肾I方4周,观察大鼠体质量、血清肿瘤坏死因子-α(TNF-α)、睾酮(T)、丙二醛(MDA)、一氧化氮(NO)、胆固醇(TC)、甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)和口服葡萄糖后2h血糖(OGTT-2hBG)和胰岛素含量以及超氧化物歧化酶(SOD)和诱导型一氧化氮合酶(iNOS)-一氧化氮合酶(NOS)活性,并计算胰岛素敏感指数(ISI)的变化。结果PCOS-MetS大鼠体质量明显增加,与空白对照组比较,差异有统计学意义(P<0.01);血清TNF-α、T、MDA、NO、TG、TC、LDL-C、FBG、OGTT-2hBG和胰岛素水平以及iNOS-NOS活性,均明显升高,而HDL-C含量、SOD活性和ISI则显著降低,与空白对照组比较,差异有统计学意义(P<0.01);二甲双胍和益肾I方高和中2个剂量均能不同程度地改善PCOS-MetS大鼠体质量增加、高雄激素血症、高血糖血症、高脂血症、高胰岛素血症和IR等病理生理改变(P<0.01或P<0.05),以及增强抗氧化酶SOD活性,抑制NOS和iNOS活性,降低MDA和NO水平(P<0.01或P<0.05)。结论益肾I方能改善PCOS-MetS大鼠胰岛素敏感性,对抗高雄激素血症和脂质代谢异常以及氧化应激-自由基损伤,并提高抗氧化能力。     

卡托普利对高血压伴代谢综合征患者胰岛素抵抗的影响

目的观察卡托普利对高血压伴代谢综合征患者胰岛素抵抗的影响。方法选择120例高血压患者为研究对象,随机分为观察组与对照组。观察组予以卡托普利治疗,对照组予以钙通道阻滞剂治疗,观察两组治疗前后血压、血脂、外周胰岛素敏感度的变化。结果两组降压治疗效果差异无统计学意义（P〉0．05）;观察组治疗后,血脂、体重指数均下降,外周胰岛素敏感度升高,而对照组上述各指标变化不显著。结论卡托普利不仅可降压,还能增加外周胰岛素敏感性,对高血压伴代谢综合征患者的治疗有着较好的应用前景。     

卡托普利对胰岛素抵抗-高血压综合征大鼠肾素及血脂的影响

目的研究卡托普利对胰岛素抵抗-高血压综合征（IRH）大鼠肾素和血脂的影响。方法用喂饲高糖高盐高脂的方法建立IRH病理模型，将大鼠随机分为模型组及卡托普利组，测定血浆胰岛素、空腹血糖、血脂、肾素以及给药前后的血压变化。结果卡托普利7mg／（kg·d）能明显降低IRH大鼠的肾素、血压、甘油三酯和总胆固醇（P〈0．05），能改善IRH的高胰岛素血症，提高低下的胰岛素敏感指数（P〈0．01）。结论卡托普利能有效增强胰岛素的敏感性，降低IRH大鼠肾素的含量，降低高血压。     

Lyon遗传性高血压大鼠:一种低肾素性高血压动物模型(英文)

This paper reviews the data which demonstrate that Lyon genetically hypertensive (LH) rats exhibit a low renin form of hypertension. Since when compared to normotensive controls, LH rats exhibit a low renin release and are salt-sensitive. Despite this, the blockade of the renin-angiotensin system normalizes the blood pressure level and the regional blood flows in LH rats. Such a discrepancy between the compulsory presence of angiotensin Ⅱ for the hypertension to develop and the low level of renin release seen in LH rats led to two hypotheses: 1) the existence of an early, short lasting increase of renin release which would be sufficient for the occurrence of a stable hypertension; 2) an hypersensitivity to the effects of angiotensin Ⅱ. The study of the long-term effects of early short lasting blockades of the renin-angiotensin system allowed to exclude the first hypothesis. Concerning a hypersensitivity to the effects of angiotensin Ⅱ, it was found to exist in the preglomerular vessels of LH rats. Th     

高血压和高血压合并糖尿病大鼠局部肾素—血管紧张素系统基因表达研究

目的：用血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)干预治疗前后，观察高血压和高血压合并糖尿病大鼠肾局部的肾素—血管紧张素系统(RAS)的基因表达变化，探讨这两类药物对肾脏保护作用的分子机制。方法：用反转录聚合酶链反应(RP-PCR)，分别对自发性高血压大鼠(SHR)和链尿菌素(STZ)诱导糖尿病合并高血压大鼠(SHR-DM)的肾皮质内血管紧张素转换酶(ACE)和血管紧张素II的I型受体(AT1）mRNA表达进行测定，并观察用依那普利或氯沙坦干预后的mRNA表达变化。结果：①基础状态下，SHR-DM肾皮质内ACE和ATl受体mRNA表达水平部显低于SHR(两组P＜0．05)，与正常血压大鼠(WKY)无差别。②在SHR—DM，用依那普利后，ACEIRNA能被抑制(P＜0．05)，但ATl受体mRNA无显变化；用氯沙坦后，ACEIRNA同样被抑制(P＜0．05)，ATl受体mRNA亦无显变化。③在SHR，用依那普利后，ACEIRNA能被抑制(P＜0．05)，但ATl受体mRNA无显变化；用氯沙坦后，ACE和ATl受体mRNA都被抑制(两组P＜0．05)。结论：高血压病和高血压合并糖尿病有着不同的病理生理机制，ACEI和ARB对糖尿病肾脏可能有不同的作用。     

高脂高盐饮食对未成年鼠生长及代谢的影响

目的 观察高脂高盐饮食对未成年鼠生长发育、胰岛素敏感性及相关代谢指标的影响. 方法 40只体质量50g左右SD鼠（生长至3周末,刚断乳）随机分为三组：普通饮食组（NC组）12只、高脂组（FC组）14只、高脂高盐组（FSC组）14只,分别给予普通食物、高脂食物、高脂＋高盐食物喂养4周（鼠生长至7周末）,观察三组大鼠体质量、血压及内脏脂肪重量、血脂等,行口服葡萄糖耐量试验及胰岛素释放试验评价血糖及胰岛细胞功能. 结果 FSC组鼠体质量、内脏脂肪、血糖及胰岛素水平均较NC组明显增加,血脂紊乱加重并表现出显著的胰岛素抵抗,差异有统计学意义（均P＜0.05）. 结论 高脂高盐饮食可诱导未成年鼠腹型肥胖、高血压、血脂异常及糖耐量异常.     

The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: a study in a rat model of moderate and relatively high human exposure

It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H₂O₂), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H₂O₂ and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.     

Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides

Oxidative stress by increased production of reactive oxygen species has been implicated in the toxicity of many pesticides. Therefore, the aim of the present study was to investigate the effect of a broad spectrum insecticide, composed of a mixture of organophosphate plus pyrethroids (fenitrothion 25%, lambda cyhalothrin 2.5% and piperonyl butoxide 6%), on antioxidant status and oxidative stress biomarkers in rat brain. Different insecticide concentrations (0, 0.1, 1, 10, 100 and 1000 mM) were incubated with brain homogenate at 37 °C for time intervals (0, 30, 60, 120, 180 and 240 min). Exposure to insecticide mixture resulted in a significant increase (p < 0.05) in thiobarbituric acid reactive substances (TBARS), which might be associated with decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and acetylcholinesterase activities and beside protein content in rat brain. However, a significant induction of lactate dehydrogenase (LDH) activities was observed. The response was concentration and time dependent. Results showed that the used insecticides had the propensity to cause significant oxidative damage in rat brain, which is associated with marked perturbations in antioxidant defense system in addition to antioxidant enzymes can be used as potential biomarkers of toxicity associated with pesticides exposure.     

非酒精性脂肪肝患者血清脂联素水平及其与氧化应激的相关性研究

目的:探讨非酒精性脂肪性肝病患者血清脂联素水平变化及其与肝功能、氧化应激的关系。方法:选取非酒精性脂肪性肝病89例,其中非酒精性脂肪性肝病合并代谢综合征47例,健康体检者30例作为正常对照组。行腹部B超检查,测量身高、体重、腰围、臀围、血压,计算体重指数、腰臀比,检测空腹血糖(FBG)、ALT、GGT、甘油三酯、高密度脂蛋白胆固醇、脂联素、丙二醛(MDA)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)等指标。并分析血清脂联素与各临床指标的关系。结果:非酒精性脂肪肝患者血清脂联素水平明显低于正常对照组,氧化应激程度明显高于正常对照组;合并代谢综合征或肝功能异常的非酒精性脂肪肝患者氧化应激程度升高更显著,而脂联素水平下降更明显;血清脂联素水平与GSH、GSH/GSSG呈明显正相关,与ALT、AST、GGT、MDA、GSSG呈明显负相关;多重线性回归分析提示GSH/GSSG、GSSG、MDA、GSH、ALT是影响血清脂联素水平的独立相关因素。结论:脂联素可能是一种间接反映氧化应激程度的监测指标,脂联素、MDA及GSH/GSSG联合检测有助于非酒精性脂肪肝病情发展的判断。     

A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia

In the present study, role of brain insulin receptors (IRs) in memory functions and its correlation with acetylcholinesterase (AChE) activity and oxidative stress in different brain regions were investigated in intracerebroventricular (ICV) streptozotocin (STZ) induced dementia model. Rats were treated with STZ (3 mg/kg, ICV) on day 1 and 3. Donepezil (5 mg/kg po) and melatonin (20 mg/kg ip) were administered in pre- and post-treatment schedules. Morris water maze test was done on day 14 and animals were sacrificed on day 21 from 1st STZ injection. Memory deficit was found in STZ group as indicated by no significant decrease in latency time antagonized by donepezil and melatonin. IR protein level was found significantly increased in trained group as compared to control, whereas STZ decreased IR level significantly as compared to trained rats in hippocampus which indicates that IR is associated with memory functions. STZ induced decrease in IR was reversed by melatonin but not by donepezil. Melatonin per se did not show any significant change in IR level as compared to control. AChE activity (DS and SS fraction) was found to be increased in hippocampus in STZ group as compared to trained which was inhibited by donepezil and melatonin. Increase in MDA level and decrease in GSH level were obtained in STZ group indicating oxidative stress, which was attenuated by donepezil and melatonin. Effectiveness of antioxidant, melatonin but not of anti-cholinesterase, donepezil against STZ induced changes in IR indicates that IR is more affected with oxidative stress than cholinergic changes.     

Can garlic oil ameliorate diabetes-induced oxidative stress in a rat liver model? A correlated histological and biochemical study

This study aimed to characterise the structural changes in liver of an alloxan-induced diabetic rat and to explain such changes in terms of the biochemical changes in free radicals and antioxidants. In addition, it aimed to determine the potential ability of garlic oil to alter these changes. The study groups were: control (n = 12), alloxan-induced diabetic rats (n = 10) and alloxan-induced diabetic rats treated with garlic oil (10 mg/kg body weight (n = 10)). Markers of oxidative stress were assessed. Small pieces of the liver were processed for transmission electron microscopic study. Garlic oil caused a significant decrease in levels of LPO in plasma (0.26 vs 0.53), erythrocyte lysate (14.4 vs 24.8) and liver tissue homogenate (1.04 vs 2.08), whereas those of thiols were significantly elevated (1.2 vs 0.46), (24 vs 15) in plasma and erythrocyte lysate respectively. SOD activity and G-S-T activity were significantly elevated in erythrocyte lysate (5.7 vs 3.3) (377 vs 179) and liver homogenate (1.4 vs 0.5) (752 vs 623) respectively after garlic oil administration. Ultrastructural study of the liver confirmed the ability of garlic to retard lipid peroxidation of cellular membranes induced by oxidative stress associated with diabetes. Therefore, garlic could normalise oxidative stress in alloxan-induced diabetic rats.     

Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in patients with essential hypertension

Objective: Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition. Patients: To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH). Results: The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+31%), HDL₂-C (-16%), and CHOL (+7.6%); in contrast TG and CHOL were unchanged after captopril in fourteen patients and their HDL₂-C declined (-16%). Neither drug altered lipoprotein core lipid composition, but small increases were observed in the HDL₂ sphingomyelin/lecithin ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin (L) ratio, a new index of cardiovascular risk, was abnormally increased before treatment and was not altered by either drug. Conclusion: These findings indicate that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein surface lipid composition in patients with EH that are confined to the HDL₂ subfraction.Supported by Grant 5446 from the Swedish Medical Research Council and a grant from Bristol Myers-Squibb     

Protective effects of selenium on oxidative damage and oxidative stress related gene expression in rat liver under chronic poisoning of arsenic

Arsenic (As) is a toxic metalloid existing widely in the environment, and chronic exposure to it through contaminated drinking water has become a global problem of public health. The present study focused on the protective effects of selenium on oxidative damage of chronic arsenic poisoning in rat liver. Rats were divided into four groups at random and given designed treatments for 20 weeks. The oxidative damage of liver tissue was evaluated by lipid peroxidation and antioxidant enzymes. Oxidative stress related genes were detected to reflect the liver stress state at the molecular level. Compared to the control and Na₂SeO₃ groups, the MDA content in liver tissue was decreased and the activities of antioxidant enzymes were increased in the Na₂SeO₃ intervention group. The mRNA levels of SOD1, CAT, GPx and Txnrd1 were increased significantly (P < 0.05) in the combined Na₂SeO₃ + NaAsO₂ treatment group. The expressions of HSP70 and HO-1 were significantly (P < 0.05) increased in the NaAsO₂ group and reduced in the combined treatment group. The results indicate that long-term intake of NaAsO₂ causes oxidative damage in the rat liver, and Na₂SeO₃ protects liver cells by adjusting the expression of oxidative stress related genes to improve the activities of antioxidant enzymes.