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1.
番茄红素对动脉粥样硬化兔血脂的调节作用   总被引:5,自引:2,他引:5  
目的研究番茄红素(lycopene)对动脉粥样硬化兔血脂的调节作用。方法21只新西兰大白兔,♀♂不拘,随机分为正常对照组、高脂模型组(胆固醇组)、番茄红素预防干预组(药物组),分别饲喂标准、标准+胆固醇、标准+胆固醇+番茄红素的颗粒饲料,于实验开始前1d和开始后第4、8、10wk末取空腹血,检测血清甘油三酯(TG)、总胆固醇(TC)和高密度脂蛋白胆固醇(HDLC)。10wk末取血后处死,取主动脉、肝脏做病理形态学观察。所有数据经SPSS10.0软件进行统计分析。结果与胆固醇组比较,药物组的TG在第10wk时降低(P<0.01)。病理分析,主动脉的苏丹Ⅳ大体观察显示,药物组的主动脉脂质斑块面积较胆固醇组减少,脂肪肝的程度也较胆固醇组减轻。结论番茄红素可以防止或延缓新西兰兔大血管动脉粥样硬化病变的形成,其机制除抗氧化以外,还可能与调血脂、降低甘油三酯浓度有关。  相似文献   

2.
The aim of this study was to investigate vascular endothelin-converting enzyme activity and the tissue level of endothelin-1 in the aorta related to atherosclerotic lesions in high cholesterol diet-fed rabbits. Rabbits were fed two atherogenic diets, 0.5% and 1.5% cholesterol, and a normal diet for 16 weeks. Vascular endothelin-converting enzyme activity in the aortic arch and thoracic aorta was significantly increased (2.0-4.4 times) by the atherogenic diet as compared with the normal diet group as well as the levels of lipids and lipid peroxide in plasma were significantly increased. Tissue endothelin-1 levels in both aortas were also elevated (2.3-6.8 times), corresponding well to the increased tissue enzyme activity. In contrast, plasma endothelin-1 levels increased only in the 1.5% cholesterol diet group (2.7 times). These results indicate that the endothelin-converting enzyme activity and the corresponding endothelin-1 level in the vascular walls increase in association with the development of atherosclerotic lesions.  相似文献   

3.
The aim of this work was to investigate the effect of sitagliptin on lipid profile and endothelium function in rabbits. Rabbits were fed either normal chow or atherogenic diet for 10 weeks. Sitagliptin (6 mg/kg/twice daily) was given orally for 6 weeks starting from week 4. Blood samples were collected at day 0, week 4, and week 10 to measure serum lipid profile, nitrate/nitrite (NOx), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels. The aortic arch and thoracic aorta were excised and used for histological study and isolated vascular preparations, respectively. Sitagliptin treatment significantly reduced the levels of low density lipoprotein cholesterol, NOx, total cholesterol, and MDA, but not triglyceridess. Additionally, sitagliptin markedly reversed the decrease in high-density lipoprotein cholesterol level. Moreover, sitagliptin significantly improved the impaired endothelium-dependent relaxation, without affecting phenylepherine-induced contraction and sodium nitroprusside-induced endothelium-independent relaxation in isolated aortic rings. Histopathological examination revealed marked reduction of the atherosclerotic lesions by sitagliptin. Immunohistochemical analysis of nuclear factor-kappa B in aortic tissue showed marked reduction in its expression upon treatment with sitagliptin compared with atherogenic diet-fed rabbits. These results suggest that sitagliptin may be an effective pharmacological approach for preventing atherosclerotic lesion progression in rabbits.  相似文献   

4.
The effect of trapidil on experimental hyperlipemia and atherosclerosis induced by 1% cholesterol diet in SPF male rabbits (JW/KBL) was investigated by the determination of the lipid contents of the plasma and thoracic aorta and examination of morphological changes in the aorta. Trapidil inhibited the increase of total lipid (TL), total cholesterol (TC), free cholesterol (FC) and phospholipid (PL) by the cholesterol diet in all groups. The level of cholesterol (HDL-C) and phospholipid (HDL-PL) in high density lipoprotein (HDL) remained unchanged after the cholesterol diet and trapidil administration. The atherogenic index (TC-HDL-C/HDL-C, PL-HDL-PL/HDL-PL) was improved by the inhibition of TC and PL by the administration of trapidil. A morphological study of the aorta showed that trapidil inhibited lipid deposition. A microscopic observation of the intima by Sudan III stain showed that inhibition of lipid deposition corresponded with the quantity of trapidil administration. An observation of aorta using transmission electron microscopy (TEM) showed that trapidil inhibited the presence of form cells due to HCD. This inhibition corresponded with the quantity of trapidil administration; and no form cells were seen in the 50 mg/kg-administered group. An observation of intima using scanning electron microscopy (SEM) showed that trapidil inhibited the irregularly elevated regions by HCD. The structure of intima in the 50 mg/kg-administered group was similar to that of the control groups. The observation of the head angiogram showed that trapidil improved the stenosis in the lingual and temporal arteries which was caused by HCD.  相似文献   

5.
目的复制动脉粥样硬化狭窄的模型,血管造影测量动脉狭窄程度以证实造模成功。方法实验于2003年2~5月在郑州大学人民医院心血管内科实验室完成。选择雄性4月龄新西兰大白兔20只,随机分为单纯饲喂高脂饮食组、高脂饮食同时动脉内膜剥脱组,每组10只。分笼饲养,饲喂正常的全价颗粒饲料,自由饮水,观察1周后进入实验。1周后所有的兔子均开始高脂饮食(含1.5%胆固醇)喂养,高脂饮食同时动脉内膜剥脱组高脂喂养3d后用股动脉穿刺法行腹主动脉内皮剥脱术。术后继续喂养同样的高脂饲料。于术后第9周行腹主动脉血管造影检查,记录腹主动脉狭窄程度。结果术后第9周进行血清总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白胆固醇测定,两组兔血清总胆固醇、甘油三酯、高、低密度脂蛋白胆固醇均升高,高脂饮食与动脉内膜剥脱组升高更明显(P<0.05)。血管造影显示所有兔的动脉粥样硬化狭窄均形成,目测狭窄程度在50%~70%[(57.000±7.888)%],狭窄长度8~23mm。结论动脉内膜剥脱术同时饲喂高胆固醇饮食可以在短时间内复制出动脉粥样硬化狭窄模型,血管造影判定血管狭窄程度。  相似文献   

6.
SUMMARY: The anti-atherosclerotic properties of F 12511, a novel acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, were studied in rabbits that were fed a cholesterol-free casein-rich diet and developed endogenous hypercholesterolemia and fibrofatty preatheroma lesions. After 6 weeks of casein feeding, an endothelial abrasion was performed in the abdominal aorta; at week 8, a control group was maintained on this diet while F 12511 (8 mg/kg/d) was administered as a diet admixture for the subsequent 24 weeks. Total plasma cholesterol level rose to 250-300 mg/dl in both groups before starting the treatment; F 12511 time-dependently reduced total plasma cholesterol by 50%, and also decreased by 50% the incidence of lesions and macrophage accumulation in uninjured aorta (thoracic arch, celiac bifurcation). Residual lesions in the treated group were characterized by few macrophages, essentially under the endothelium, and by a larger content of smooth muscle cells. Quantitative image analysis of serial sections of mechanically injured abdominal aorta revealed a 20% surface covered by preatheroma lesions in the placebo group; F 12511 significantly reduced this surface. These data suggest that the combination of endogenous hypercholesterolemia with endothelial injury in the rabbit may offer a useful model to study atherosclerosis; lipid lowering by F 12511 reduces the incidence of vascular lesions and macrophage infiltration and may reinforce the fibrous skeleton of the atheroma.  相似文献   

7.
目的 探讨贻贝多糖MA对实验性动脉粥样硬化兔的降血脂作用及其机制,并观察其对肝脏和主动脉的影响.方法 采用喂养高脂饲料的方法建立实验性动脉粥样硬化兔模型,连续给予MA 4周后,测定兔血脂水平,如血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、高密度脂蛋白胆固醇(HDL)水平,以及与血脂代谢相关酶如脂蛋白酯酶(LPL)、肝酯酶(HL)、羟甲基戊二酸单酰辅酶-A还原酶(HMG-CoAR)活性;并进行肝脏的病理组织学和超微结构检查;油红染色观察兔主动脉粥样硬化斑块的脂质沉积情况.结果 贻贝多糖MA能显著降低实验性动脉粥样硬化兔血清TG、TC、LDL水平,并显著增加HL和LPL的活性(P<0.05).MA能减轻肝脏脂质沉积,减少主动脉粥样硬化斑块的脂质沉积和斑块形成.结论 贻贝多糖MA通过增加HL和LPL活性发挥调血脂功能,可用于防治家兔动脉粥样硬化和脂肪肝.  相似文献   

8.
<正> 在动脉粥样硬化(AS)的发生发展中,钙几乎参与了每个环节,细胞内钙超载能诱发和加速病变的形成.新二氢吡啶类钙拮抗剂尼索地平能减轻动脉粥样硬化斑块,间尼索地平与尼索地平的药理作用基本相同.本实验观察了间尼索地平对兔实验性动脉粥样硬化的作用,并与尼索地平进行比较.  相似文献   

9.
李韬  雷菠  冯丽芬  韦耀东 《江苏医药》2012,38(7):763-765
目的探讨三七粉对高脂血症家兔的降脂作用及对血浆血栓烷B2(TXB2)、α-颗粒膜蛋白140(GMP-140)含量的影响。方法 18只健康家兔随机均分为高脂血症组(A组)、高脂血症治疗组(B组)和对照组(C组)。A、B组饲喂高脂饲料,C组饲喂普通饲料,共6周。第3周开始,B组灌服三七粉0.23g.kg-1.d-1,A、C组灌以等体积的生理盐水。分别于实验前、第3、6周时检测血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)水平,第6周时检测血浆中TXB2、GMP-140含量。结果与A组相比,第6周时B组血清TG、HDL-C水平明显下降(P<0.05),血浆TXB2、GMP-140含量显著降低(P<0.01)。结论三七能降低血脂,抑制TXB2、GMP-140表达,对动脉粥样硬化和血栓性心脑血管疾病有较好的防治作用。  相似文献   

10.
The hypolipidemic and antiatherosclerotic effects of NIP-200 (3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-th ion e) were studied in experimental models of 1% cholesterol diet (HCD)-fed rabbits. The increases of total lipids, total cholesterol (TC), free cholesterol (FC) and phospholipid (PL) in plasma by HCD-feeding were inhibited by the treatment of NIP-200. The plasma contents of TC in high density lipoprotein (HDL-TC) and HDL-PL in the treatment of NIP-200 were increased more than that of the control and the HCD-fed group, but the former was not significantly different compared to the HCD-fed group. Both atherogenic index using TC-HDL-TC/HDL-TC and PL-HDL-PL/HDL-PL were reduced by NIP-200. There was a slight deposition of fatty plaques on the lumen surface of the thoracic aorta in the HCD-fed and NIP-200-treated rabbits. In the scanning electron microscopic study on the lumen surface of the aortic arch, NIP-200 reduced fatty plaques. NIP-200 also prevented the loss of endothelial fissures and swelling of the nuclei. It is suggested that the hypolipidemic action of NIP-200 may be the inhibition of lipid absorption in the intestine and the acceleration of lipid excretion in the liver. The antiatherosclerotic action of NIP-200 may be due to the improvement of lipid metabolism by the increases of HDL-TC and HDL-PL in plasma.  相似文献   

11.
葡萄籽原花青素对动脉粥样硬化兔血脂的调节作用   总被引:18,自引:2,他引:18  
目的 研究葡萄籽原花青素 (GSP)对动脉粥样硬化(AS)兔血脂的调节作用。方法  2 4只♂新西兰大白兔随机分为正常对照 (A)组、高脂模型 (B)组、GSP预防干预 (C)组 ,分别饲喂标准、标准 + 1%胆固醇、标准 + 1%胆固醇 + 1%GSP的颗粒饲料 ,于实验开始前 1d和开始后第 1、2、4、8、12wk末取空腹血 ,检测血清甘油三酯 (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)。 12wk末取血后处死 ,取主动脉作病理形态学观察。所有数据经SAS 8 2进行混合模型的变异数分析。结果 与B组比较 ,C组TC、LDL C、TG和TG/HDL C在 12wk时降低 (P <0 0 1) ,HDL C升高 (P <0 0 5)。病理分析显示C组兔主动脉壁厚度和泡沫细胞数量明显较B组减轻 (P <0 0 1)。结论 GSP对血脂有调节作用 ,可通过降低TC、LDL C、TG、TG/HDL C和升高HDL C的作用而发挥抗AS作用 ,并有可能改善胰岛素抵抗状态  相似文献   

12.
目的探讨吡格列酮对高脂饮食下兔主动脉血管内皮细胞黏附分子(VCAM)-1表达的影响。方法设立正常饮食、高脂饮食及高脂饮食加吡格列酮干预3组,通过比较主动脉病理形态学改变、血脂的变化、VCAM-1分子的表达进行研究,采用苏木素-伊红染色用于主动脉病理形态学观察,采用免疫组织化学检测兔主动脉上VCAM-1的表达。结果吡格列酮能减轻高脂饮食所致的内膜增厚和平滑肌增生。吡格列酮还能明显升高高密度脂蛋白胆固醇(HDL),对总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、甘油三酯(TG)无明显影响。高脂饮食刺激兔主动脉VCAM-1的表达增加,吡格列酮能显著减轻这种作用(0.78±0.16vs0.42±0.11,P<0.01)。结论吡格列酮能减轻高脂饮食兔主动脉VCAM-1的表达,其作用的机制可能与其干扰核转录因子有关。  相似文献   

13.
The effects of eicosapentaenoic acid ethylester (EPA-E) at daily doses of 3 and 30 mg/kg (p.o.) on vascular lesions and changes in blood components were investigated in rabbits fed with a 1% cholesterol diet for 12 weeks and partly compared with those given 30 mg/kg/day (p.o.) of ticlopidine. EPA-E at 30 mg/kg significantly improved the reduction in distensibility of isolated thoracic aorta caused by cholesterol diet feeding. Ticlopidine at 30 mg/kg also showed significant but milder improvement. EPA-E at 30 mg/kg, unlike ticlopidine, tended to lower cholesterol content in the thoracic wall and elastin fraction. Although EPA-E did not act on plasma total cholesterol, HDL-cholesterol and triglyceride contents, it tended to mildly reduce platelet aggregability in response to sodium arachidonate and the increased production of TXA2-like activity by platelets. In addition, daily doses of 30 mg/kg EPA-E caused a significant increase in plasma and platelet EPA-E contents without any change in docosahexaenoic acid and arachidonic acid contents. From these results, daily administration of EPA-E to cholesterol diet-fed rabbits caused a remarkable improvement of the reduction in distensibility of isolated thoracic aorta. The mechanism of this improvement by EPA-E appears to depend on the protection of elastic fibers from lipid deposition on the vascular wall.  相似文献   

14.
Exposure of rabbits for 12 weeks to 300 ppm carbon disulfide (CS2) for 6 h/day, 5 days/week, or to 25 mg/day of thiourea or 2% cholesterol in the diet, or to any combination thereof caused a significant reduction in the concentration of serum thyroxine (T4). The reduction of the concentration of serum T4 in rabbits by the treatments was completely offset by the inclusion of 0.1 mg/day of sodium levothyroxine in the diet. Ingestion of feed containing 2% cholesterol significantly increased the degree of atherosclerosis present in the aortic arch and significantly increased the oil red O positive lipid present in the heart and the aorta, with the aortic arch being the most severely affected. The response of the aorta and the heart to the 2% cholesterol diet was not significantly modified by concurrent exposure to CS2 by inhalation or by treatment with thiourea, a metabolite of CS2. We found no evidence that the development of cardiovascular lesions induced by a 2% cholesterol diet in rabbits was mediated by a mechanism involving a component of hypothyroidism.  相似文献   

15.
董平  麻春杰  韩雪梅  王滨 《中国医药》2011,6(11):1296-1298
目的 观察额尔敦-乌日勒对动脉粥样硬化(AS)家兔血清中一氧化氮(NO)含量和抗氧化酶活性的影响.方法 采用喂饲高脂饲料构建家兔AS模型,将36只家兔完全随机分为4组,每组9只.正常对照组喂普通饲料,其他3组喂高脂饲料.正常组与模型组分别灌胃蒸馏水,辛伐他汀组给予辛伐他汀5 mg/( kg?d),额尔敦-乌日勒组给予额尔敦-乌日勒0.4 g/(kg?d),连续90d.检测家兔血清中NO含量,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)含量,并且测定血清TC、TG、LDL-C、HDL-C的含量,计算各组兔主动脉粥样硬化斑块面积比.结果 与模型组相比,额尔敦-乌日勒能提高AS家兔血清中NO[(231.26±44.92) μmol/L]含量,同时增强SOD[(57.81±7.65)kU/L]、CAT[(25.71±4.60) kU/L]和GSH-Px[(515.55±81.36) kU/L]的活性(P<0.05),同时降低MDA[(22.27±11.43) μmol/L]的含量(P<0.05).并且降低血清TC、TG、LDL-C水平和主动脉斑块面积比(P<0.05).结论 额尔敦-乌日勒可通过增加血清中NO含量保护血管内皮功能;通过增强机体抗氧化酶的活性,提高抗氧化能力以及通过调节血脂而起到抗AS作用.  相似文献   

16.
R-755 (N-(2,6-diethylphenyl)-N'-[3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[f[l]benzothiophen-2-yl]urea), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, has been characterized in vitro, ex vivo and in vivo. R-755 potently inhibited ACAT activities, with IC50 values from 2.5 to 64 nM, in rabbit intestinal microsomes and several cell lines (CaCo-2, THP-1 and J774A.1 cells). R-755 reduced serum cholesterol and triglyceride levels and liver cholesterol contents in cholesterol-fed rats, hamsters and rabbits. Rabbits were fed a high cholesterol diet for 2 weeks and further fed the same diet containing R-755 for 2 weeks. R-755 dose-dependently reduced cholesterol content and ACAT activity in the aorta. When phorbol 12-myristate 13-acetate-treated THP-1 and J774A.1 cells were incubated in the medium containing 20% of serum from rats administered R-755, the ACAT activities of the cells were inhibited. Rabbits were fed a high cholesterol diet for 8 weeks to establish aortic atherosclerosis and then fed a normal diet with or without R-755 for 8 weeks. R-755 dose-dependently reduced the surface area with atherosclerotic involvement and cholesterol contents in the aorta, although plasma cholesterol level did not differ from that in the control group. These results suggest that R-755 is a potent hypolipidemic agent and has a direct antiatherosclerotic activity at the arterial wall.  相似文献   

17.
PPARγ激活剂罗格列酮对兔动脉粥样硬化斑块消退的影响   总被引:2,自引:0,他引:2  
王朝晖  罗丰  刘小楣 《药学学报》2005,40(11):1051-1053
过氧化物酶体增殖激活受体γ(PPARγ)是一个核受体,在血管壁内皮细胞、巨噬细胞/泡沫细胞及血管平滑肌细胞都有较高表达。PPARγ通过对这些细胞的调控作用,还影响着炎性因子的水平,在动脉粥样硬化(AS)疾病中发挥着重要的作用[1]。本实验通过高选择性PPARγ激动剂罗格列酮对高胆  相似文献   

18.
1. The in vivo pharmacological effects of scoparone (6,7-dimethoxycoumarin) in a hyperlipidaemic diabetic rabbit model were investigated. 2. Three groups of rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic-untreated and (3) hyperlipidaemic and diabetic-scoparone treated. The hyperlipidaemic diabetic rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic agent. The plasma levels of total cholesterol, total triglyceride, very low-density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were markedly increased as soon as the rabbit became diabetic at the second week. Scoparone-treatment (5 mg kg-1 day-1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol, 48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol and 79.5% of HDL cholesterol. 3. Six weeks after cholesterol-feeding, the aortic arch and thoracic aorta were dissected for morphological and functional studies. In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was intimal thickening with accumulation of fatty streaks, foam cells and migration of smooth muscle cells to the intima. In the rabbits treated with scoparone, there were fewer pathological morphology changes found in vascular segments than in the untreated hyperlipidaemic diabetic rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

19.
1. The effects of fluvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the vascular angiotensin converting enzyme (ACE) activity in hyperlipidaemic rabbits were compared with those of enalapril, an ACE inhibitor. 2. Rabbits were fed a 1.5% cholesterol containing diet or normal diet for 16 weeks and treated with either fluvastatin or enalapril in the diet at the respective doses of 2 and 10 mg kg-1 day-1. The total cholesterol, triglyceride and phospholipid levels in serum were significantly increased in rabbits fed the high cholesterol diet. Treatment with fluvastatin but not enalapril resulted in a decrease in serum lipids. 3. The vascular ACE activities assessed via the cleavage rate from synthetic substrate in the aortic arches and upper thoracic aortae were increased by 8 to 10 times when the rabbits were made hyperlipidaemic. Fluvastatin as well as enalapril significantly lowered the tissue ACE in the aortae. 4. The ACE activities in serum did not alter in hyperlipidaemic rabbits either in the presence or absence of fluvastatin. The serum ACE activity was lowered by enalapril. 5. The lipid peroxide in serum as well as the plaque area in the thoracic aorta was significantly increased in the cholesterol diet-fed rabbits. Treatment with fluvastatin or enalapril reduced both serum lipid peroxide and plaque formation. The relaxant responses to acetylcoholine (ACh) were significantly suppressed in the cholesterol-fed rabbits. Treatment with fluvastatin or enalapril significantly reversed the suppression of ACh-induced relaxation. 6. It seems that the reduction of vascular ACE is not coupled to lipids and ACE activity in serum, but rather to lipid peroxidation. Thus, the decrease in vascular ACE activity by fluvastatin as well as the lipid-lowering effect may reduce the risk of atherosclerosis progression in the vasculature.  相似文献   

20.
目的探讨金粉蕨素对实验性动脉粥样硬化兔血脂的影响。方法 21只健康大耳白兔,随机分为3组,分别给予正常饲料、高脂饲料、高脂饲料加金粉蕨素,观察8周,测定兔血浆中TC、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量,并且观察三组实验动物的主动脉病理学形态改变。结果对动脉粥样硬化兔给予金粉蕨素可以明显降低兔血浆中TG、TC、LDL-C含量,差异具有统计学意义(P<0.05),而且金粉蕨素可有效减小高脂饲料引起的兔动脉粥样硬化斑块面积。结论金粉蕨素具有较强的抗动脉粥样硬化作用,给予金粉蕨素治疗8周,胆固醇含量明显下降。深入探讨金粉蕨素的作用机制将为动脉粥样硬化的治疗及新药开发提供新的思路。  相似文献   

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