肝旺痰阻型高血压大鼠模型的建立和评价研究

目的：建立和评价肝旺痰阻型高血压大鼠模型。方法：采用自发性高血压大鼠,以长期激怒联合高质饮食法建立肝旺痰阻的复合证候。通过观察大鼠性情动态的变化及体重、血压及血脂和血管紧张素II的变化,对高血压大鼠肝旺痰阻证型进行综合评价。结果：模型组大鼠在性情动态及体重、血压、血脂和血管紧张素II等方面均与对照组有较大差异（P〈0．05）,符合了中医肝旺痰阻证型的表现。结论：采用自发性高血压大鼠,以长期激怒联合高质饮食法,可建立肝旺痰阻型高血压大鼠动物模型。     

葛根素对肥胖型高血压大鼠血压和血管功能影响的实验研究

目的:本研究旨在观察饮食中添加葛根素对肥胖型高血压大鼠的心血管代谢指标的影响,尤其关注其对于血压和血管功能的效应。方法:①自发性高血压大鼠24只,分正常饮食对照组(8只)、高脂饮食组(8只)、高脂饮食+葛根素组(8只),大鼠先进行1周的适应性喂养,1周后进行干预,干预时间为14周;②每周测1次体重、鼠尾血压;③实验结束时空腹取血浆测血脂、血糖值,取胸主动脉观察主动脉的内皮依赖性及非内皮依赖性舒张功能。结果:①葛根素可防止高脂饮食导致的自发性高血压大鼠体重的增加及血压、血糖的升高,与高脂饮食组比较,P<0.05或P<0.01。②长期葛根素喂养可有效防止高脂饮食导致的高血压大鼠的血脂水平升高;③长期的葛根素喂养可显著改善肥胖型高血压大鼠的血管舒张功能及降低血压。结论:葛根素可有效改善肥胖型高血压大鼠的相关代谢指标,并可明显降低血压及改善血管功能,提示葛根素对肥胖型高血压有较好的防治作用,值得进一步深入研究。     

内源性中枢血管紧张素Ⅱ在慢性应激大鼠血压高反应性中的作用

心理生理学研究表明,高血压病人对应激刺激的反应性要高于正常血压者,高血压息者对刺激产生的血压变化在幅度与时限上均强于正常血压者。动物实验表明,与Wistar-Kyoto(WKY)大鼠相比,自发性高血压大鼠(SHR)对环境心理应激的心血管反应性增强,并可能与遗传有关。在SHR的高血压维持中血管紧张素Ⅱ(AⅡ)起一定作用。本实验探讨内源性中枢AⅡ在慢性应激Wistar大鼠动脉血压高反应     

有氧运动上调Agtr1a基因甲基化改善高血压肠系膜动脉ACE1-AT1R收缩轴功能

血管紧张素Ⅱ 1A受体(angiotensin Ⅱ type 1A receptor, AT1aR)是Ang Ⅱ的主要受体亚型。AT1aR基因(Agtr1a)启动子区DNA甲基化水平的变化是调控AT1aR表观遗传的重要机制。为明确运动是否通过调节Agtr1a基因启动子区甲基化水平而减弱ACE1-AT1R收缩轴功能,从而起到改善高血压血管功能的作用,本研究选用3月龄自发性高血压大鼠(spontaneously hypertensive rat, SHR)和正常血压对照组大鼠(Wistar-Kyoto, WKY),随机分为正常血压安静组WKY-C、正常血压有氧运动组WKY-E、高血压安静组SHR-C、高血压有氧运动组SHR-E,各组n=24。12周跑台运动结束后,有氧运动显著减低运动组大鼠血压和体重(P0.05);采用微血管环张力测定技术测定肠系膜动脉对去甲肾上腺素(norepinephrine, NE)、血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)的反应性。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P0.05);高效液相色谱法(high performance liquid chromatography, HPLC)测定血浆中ACE1-AT1R收缩轴主要活性肽血管紧张素原(angiotensinogen, AGT)、AngⅡ的水平。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P0.05);免疫印迹法和q-PCR技术测定肠系膜动脉ACE1、AT1R蛋白质和AT1aR的mRNA水平相对含量。结果显示,有氧运动显著降低高血压大鼠肠系膜动脉ACE1、AT1R蛋白质和AT1aR mRNA水平(P0.05);亚硫酸氢盐测序BSP法测定Agtr1a基因的启动子区甲基化水平。结果显示,有氧运动显著上调高血压大鼠肠系膜动脉Agtr1a基因启动子区甲基化水平(P0.05)。本研究表明,有氧运动通过上调高血压肠系膜动脉Agtr1a基因启动子区甲基化水平,即而减弱RAS系统ACE1-AT1R收缩轴功能,从而抑制高血压血管张力增高,缓解血压增高。     

镁离子联合金雀异黄素对自发性高血压大鼠血压的影响

目的:探讨镁离子联合金雀异黄素对自发性高血压大鼠血压的影响。方法:选用雌性6周自发性高血压大鼠28只,饲养7d后测量大鼠初始收缩压(SBP)及心率(HR),应用双盲分组原则,将大鼠分成对照组、镁离子组、金雀异黄素组、及联合组,每组各7只。饲养7d后,取一次性注射器,消毒抽取药物,暴露尾部及血管,进行注射。每7d注射一次,连续注射4周。比较各组大鼠SBP、HR、hs-CRP、MCP-1、vWF、血管紧张素(AngⅡ)。结果:给药前四组大鼠SBP水平比较无差异(P0.05)。给药后对照组SBP水平高于其他三组(P0.05),镁离子组与金雀异黄素组比较无差异(P0.05),联合组大鼠在给药1周、2周、4周后SBP水平显著低于其他三组(P0.05)。给药前四组大鼠心率比较无差异(P0.05)。给药后对照组、镁离子组、金雀异黄素组与治疗前相比无差异(P0.05),联合组低于治疗前(P0.05)。给药第2、4周联合组HR水平低于其他三组(P0.05)。联合大鼠hs-CRP水平显著降低(P0.05),MCP-1、vWF水平显著升高(P0.05)。给药前各组大鼠AngⅡ水平比较无差异(P0.05),给药2周、4周联合组AngⅡ水平显著降低(P0.05)。结论:镁离子联合金雀异黄素能提高自发性高血压大鼠血管顺应性,减少炎症反应,预防动脉粥样硬化,降低血压。     

慢性低氧时自发性高血压大鼠血浆心钠素、肾素—血管紧张素系统与血液动力学的变化

实验采用同龄自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY),各随机分为对照组(N)和低氧组(H)。实验前 SHR 尾动脉压(25.4±2.6kPa,n=20)明显高于WKY(13.1±1.6kPa,n=20),P<0.001。SHR-N组血浆心钠素(ANP)、血管紧张素Ⅱ(AⅡ)含量和肾素活性(RA)明显高于WKY-N。SHR-N经实验两周后血压自然上升(P<0.01)。SHR和WKY缺氧后ANP、AⅡ、RA各值均比各自对照值增加,但血压无明显改变.而肺动脉压均明显升高。以上结果提示,SHR 大鼠慢性缺氧后,ANP和肾素-血管紧张素系统可能对防止血压上升和限制肺动脉高压进一步发展起一定的调节作用。     

压力超负荷大鼠心肌内分泌因子活化及相互作用

目的：探讨压力超负荷是否诱导心肌内分泌活化及相互间的作用。方法：用放免法及比色法检测腹主动脉缩窄高血压大鼠心肌组织中血管紧张素Ⅱ、内皮素和一氧化氮含量的变化,并观察卡普托利对它们的作用。结果：腹主动脉缩窄大鼠动脉血压逐渐升高,术后４ ｈ 即显著升高;术后３０ ｍｉｎ 心肌组织中血管紧张素Ⅱ含量显著升高,此后并保持在高水平;心肌内皮素含量于术后２４ ｈ 开始并持续显著升高;心肌中一氧化氮含量却于术后１０ ｍｉｎ 迅速显著降低并持续受抑。小剂量卡普托利对大鼠血压无明显影响,但可完全抑制心肌中血管紧张素Ⅱ的升高,而且使内皮素活化滞后、一氧化氮含量降低减轻。结论：压力超负荷可诱导心肌血管紧张素Ⅱ、内皮素含量升高及一氧化氮含量降低,而心肌血管紧张素Ⅱ可加速内皮素活化、加重一氧化氮含量降低     

易卒中型自发性高血压大鼠中枢和血管中血管紧张素Ⅱ与血压变化关系

工作分析了不同年龄易卒中型自发性高血压大鼠（SHRSP）主动脉中血管紧张素Ⅱ（AⅡ）含量与收缩压（SBP）间的关系。SHRSP的SBP在12及16周龄时均持续上升,20周龄时不再继续上升但维持在高水平;三个年龄组的SHRSP的主动脉AⅡ含量均明显高于同年龄WKY对照鼠,向SHRSP侧脑室灌注巯甲丙脯氨酸四周不仅降低脑区中AⅡ含量,而且具有明显降压效应,同时显著降低主动脉AⅡ含量及血浆、主动脉中去甲肾上腺素和肾上腺素水平,上述结果证实了SHRSP血管中肾素-血管紧张素系统活动的异常与高血压发病学间的密切关系,提示中枢AⅡ可能通过易化外周交感-肾上腺系统活动调节血管中AⅡ水平。     

怀菊花总黄酮对自发性高血压大鼠的降压作用及机制研究

研究怀菊花总黄酮对自发性高血压大鼠(SHR)的降压作用及其机制。将SHR随机分为模型组、怀菊花总黄酮高、中、低剂量组和依那普利阳性对照组。采用无创血压计测定血压及心率,采用放射免疫法测定血浆内皮素(ET)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、肾素活性(PRA)含量。结果表明怀菊花总黄酮能够降低SHR的血压(P0.01)、心率(P0.05)、血浆ET(P0.05)、AngⅡ(P0.01)、ALD(P0.01)、PRA(P0.01),其降压机制可能与改善内皮功能和抑制肾素-血管紧张素-醛固酮系统(RAAS)活性有关。     

新型抗高血压活性肽GAP-A的一级结构及生理活性研究

研究了新型乳酪蛋白源抗高血压活性肽GAP-A的分子量与一级结构,并检测了其对体外血管紧张素转化酶(ACE)的抑制活性及体内降血压效果。结果显示:抗高血压活性肽GAP-A分子量为M2,氨基酸序列为B1-B2-B3;GAP-A在体外对ACE有很强的抑制活性,抑制率为79.6%;GAP-A对自发性高血压大鼠(spontaneously hypertensive rats,SHR)有显著的降血压作用,而对血压正常的SD大鼠的血压没有影响。     

Omega-3 polyunsaturated fatty acid supplementation reduces hypertension in TGR(mRen-2)27 rats

To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)-mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II activity) were maintained on a diet either deficient or sufficient in omega-3 PUFA from conception. Half the animals on each diet were treated with the angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed the omega-3 PUFA deficient diet were significantly more hypertensive than those fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body weight, body fat and plasma leptin were reduced by perindopril treatment but not affected by omega-3 PUFA supply. Given that the elevated blood pressure of the Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce hypertension via the renin-angiotensin system.     

非酒精性脂肪肝病大鼠肝脏SOCS-3 的表达与吡格列酮干预研究

目的:探讨SOCS-3在非酒精性脂肪肝病(NAFLD)发病中的作用以及吡格列酮的干预作用。方法:29只雄性SD大鼠随机分为正常对照组(8只),高脂饮食组(21只)。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组(8只);吡格列酮干预组(8只),予以吡格列酮3mg·kg-·1d-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3 mRNA和SREBP-1c mRNA表达及肝脏病理学。结果:与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3 mRNA、SREBP1c mRNA表达显著上调。吡格列酮干预组SOCS-3 mRNA、SREBP-1c mRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3 mRNA表达水平与胰岛素抵抗指数、SREBP-1c mRNA表达水平、肝脂肪变成显著正相关。结论:SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-1c mRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。     

实验性鸡脂肪肝出血综合征模型的建立与评价

目的 建立一种造模时间较短、成本较低,成功率更高的鸡脂肪肝出血综合征动物模型.方法 320只14日龄青脚麻鸡随机分为对照组、高脂模型组、雌激素模型组和高脂结合雌激素模型组,每组设4个重复,每个重复20只,共处理28 d.期间每天观察记录鸡的临床状况,并于实验14、28 d测定血清生化指标、肝脏相关参数以及腹腔脂肪重、肝脏病理形态学变化.结果 对照组在28 d内未发生脂肪肝出血综合征,而高脂结合雌激素模型组在实验14 d发生了脂肪肝出血综合征.临床观察见10d后部分鸡开始出现张口呼吸、嗜睡、腹部大而下垂等临床表现.14 d及28 d后,剖检见腹腔脂肪过度沉积,肝脏明显肿大、黄染、质脆、边缘钝厚、表面可见散在点状或斑状出血;14 d后,显微镜下可见肝细胞轻度变性,胞质内出现较小的脂肪空泡.28 d后,可观察到大量肝细胞体积极度肿大,胞质内充满较大的脂肪空泡,肝脏结构紊乱等病理学变化;28 d后FLHS发生率高于14 d.血清甘油三酯浓度、总胆固醇浓度、肝脏相对重、腹脂相对重、肝脂率、肝出血分数与对照组相比,差异皆有显著性(P＜0.05或P＜0.01).雌激素模型组和高脂模型组的临床症状、剖检特征、病理组织学变化及血液生化指标的变化趋势与高脂结合雌激素模型组相似,但程度稍轻、发生时间较晚.结论 通过28 d的高脂日粮与雌激素复合诱导,可成功建立鸡脂肪肝出血综合征模型.     

Beneficial Effects of Calcitriol on Hypertension,Glucose Intolerance,Impairment of Endothelium-Dependent Vascular Relaxation,and Visceral Adiposity in Fructose-Fed Hypertensive Rats

Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose tolerance, and visceral adiposity in fructose-fed rats.     

Overeating of palatable food is associated with blunted leptin and ghrelin responses

Palatable food is rich in fat and/or sucrose. In this study we examined the long-term effects of such diets on food intake, body weight, adiposity and circulating levels of the satiety peptide leptin and the hunger peptide ghrelin. The experiments involved rats and mice and lasted 5 weeks. In rats, we examined the effect of diets rich in fat and/or sucrose and in mice the effect of a high fat diet with or without sucrose in the drinking water. Animals fed with the palatable diets had a larger intake of calories, gained more weight and became more adipose than animals fed standard rat chow. Fasted animals are known to have low serum leptin and high serum ghrelin and to display elevated serum leptin and lowered serum ghrelin postprandially. With time, a sucrose-rich diet was found to raise the fasting level of leptin and to lower the fasting level of ghrelin in rats. A fat-rich diet suppressed serum ghrelin without affecting serum leptin; high sucrose and high fat in combination greatly reduced serum ghrelin and raised serum leptin in the fasted state. The mRNA expression of leptin in the rat stomach was up-regulated by sucrose-rich (but not by fat-rich) diets, whereas the expression of ghrelin seemed not to be affected by the palatable diets. Mice responded to sucrose in the drinking water with elevated serum leptin (fasted state) and to all palatable diets with low serum ghrelin. The expression of both leptin and ghrelin mRNA in the stomach was suppressed in fasted mice that had received a high fat diet for 5 weeks. We conclude that the expression of leptin mRNA in stomach and the concentration of leptin in serum were elevated in response to sucrose-rich rather than fat-rich diets, linking leptin with sucrose metabolism. In contrast, the expression of ghrelin and the serum ghrelin concentration were suppressed by all palatable diets, sucrose and fat alike. In view of the increased body weight and adiposity neither elevated leptin nor suppressed ghrelin were able to control/restrain the overeating that is associated with palatable diets.     

高糖高脂致大鼠非酒精性脂肪肝合并高血糖动物模型的研究

目的建立饮食诱导非酒精性脂肪肝病（NAFLD）合并高血糖动物模型并观察其特点。方法将64只SD大鼠随机分为2组。正常对照组（用普通饲料饲喂）32只,高糖高脂组（饲以高糖高脂饲料）32只,连续喂养12个月。于实验第3月末、第6月末、第9月末、第12月末观察动物体重、内脏脂肪重量;比较血液中有关血脂、血糖、炎症介质等方面的生化指标以及组织病理学观察。结果与正常对照组相比,各阶段高糖高脂组大鼠体重、内脏脂肪重量明显增加;血清ALT、FFA、LPS、TNFα、FPG、FINS和HOMA-IR的水平都升高,其差异有统计学意义;而HOMA-β以第六个月出现代偿性增强后进行性衰退。病理组织学显示肝脏发生严重的脂变、脂肪肝进而发生肝炎、纤维化及肝硬化;随时间进展胰岛逐渐萎缩并伴有炎性浸润;脂肪细胞逐渐增大并伴有炎性浸润。结论高糖高脂饮食可建立大鼠NAFLD合并高血糖动物模型,该模型可在NAFLD和相关的糖尿病研究中发挥作用。     

多因素复合制作气虚血瘀证脑缺血动物模型的实验研究

目的通过复制气虚血瘀证型大鼠脑缺血动物模型,探索病证结合动物模型制作方法.方法选用老年Wistar大鼠,采用饥饿、疲劳、寒湿、惊恐、高脂饮食等多因素复合方法复制气虚血瘀证动物模型,采用双侧颈总动脉结扎复制脑缺血动物模型.结果通过对一般体征和微观指标的观测,发现模型大鼠基本符合中医气虚血瘀证候特点和现代医学脑缺血病理变化规律.[HTH〗结论多因素复合作用可成功复制病证结合动物模型,本动物模型有可能成为将来中医药防治脑缺血科研工作的实验基础.     

Enzymatic and metabolic responses to affluent diet of two diabetes-prone species of spiny mice: Acomys cahirinus and Acomys russatus

The adaptive responses to sucrose and fat diets were investigated in two species of spiny mice, Acomys russatus and Acomys cahirinus, in relation to their propensity to develop diabetic-like symptoms. A russatus gained weight pronouncedly, both on regular and fat-rich seed diet, did not exhibit hyperglycemia or hyperlipidemia but had highly increased hepatic triglyceride content in association with high levels of circulating free fatty acids and incidence of ketonuria in 10 of 41 animals. On the other hand, A. cahirinus exhibited a moderate weight gain on the fat diet which was accompanied by hyperglycemia but no hyperlipidemia or ketonuria. Neither weight gain nor ketonuria were evident in A. russatus and A. cahirinus on the sucrose-rich diet, but there was hyperlipidemia in the latter species. A. cahirinus, in particular, showed many-fold induction of liver enzymes, of regulatory importance in the pathways of glycolysis and lipogenesis, which could be linked to the hyperlipidemia in this species. On the fat diet there was a smaller increase in activity in enzymes related to gluconeogenesis in A. russatus compared with A. cahirinus, as well as a smaller suppression of glycolytic and lipogenic enzymes. Adipose tissue lipoprotein lipase activity rose in response to the fat-rich diet, more markedly in A. russatus than A. cahirinus in correlation to the more marked weight gain and hyperinsulinemia in this species. The affluent diets, especially sucrose, elicited an increase in circulating triiodothyronine levels which was more pronounced in A. cahirinus than in A. russatus.(ABSTRACT TRUNCATED AT 250 WORDS)