Keishi‐bukuryo‐gan prevents the progression of atherosclerosis in cholesterol‐fed rabbit

In this study, we examined whether in vivo keishi‐bukuryo‐gan (a Kampo formulation) could prevent the progression of atherosclerosis in cholesterol‐fed rabbits, an animal model for hypercholesterolaemia. Sixteen male Japanese white rabbits (2 kg body weight) were divided into two groups. Group A (n = 8) was fed standard rabbit chow containing 1% cholesterol for 8 weeks. Group B (n = 8) was fed standard rabbit chow containing 1% cholesterol and 1% keishi‐bukuryo‐gan for 8 weeks. At the end of the experiment, average plasma concentrations of total‐cholesterol and IDL‐cholesterol were 2055.9 ± 201.8 mg/dL and 408.1 ± 62.6 mg/dL in group A and 1950.5 ± 126.3 mg/dL and 407.6 ± 56.6 mg/dL in group B, respectively. The percentage of the surface area of the total thoracic aorta with visible plaque was significantly reduced by keishi‐bukuryo‐gan administration; group A was 33.2% ± 5.3% and group B was 14.3% ± 2.9%. β ‐very low density lipoprotein (VLDL) and low density lipoprotein (LDL) isolated from cholesterol fed rabbits treated with keishi‐bukuryo‐gan (group B) were shown to be highly resistant to oxidative modification by cupric ion. Sera isolated from rabbits administered keishi‐bukuryo‐gan had reduced lipid peroxide formation compared with those from rabbits without keishi‐bukuryo‐gan. Thus, keishi‐bukuryo‐gan prevents the progression of atherosclerosis in cholesterol‐fed rabbits in vivo by limiting oxidative LDL modification. Copyright © 1999 John Wiley & Sons, Ltd.     

芎芍胶囊对兔动脉粥样硬化模型脂质代谢及血小板聚集的影响

目的 观察芎芍胶囊对兔动脉粥样硬化模型脂质代谢及血小板聚集的影响并探讨其可能机制。方法 用4F·Forgarty导管剥脱损伤腹主动脉内皮后继喂高胆固醇饲料的方法,复制节段性兔动脉粥样硬化模型。70只动物术后随机分为7组,即模型3天、2周、6周组(A、B、C组),单纯内皮损伤组（D组）,普罗布考组(E组),芎芍胶囊小剂量组（F组）,芎芍胶囊大剂量组（G组）,另10只为假手术组（N组）。除D组和N组外,其余各组均在高胆固醇饲料基础上分别喂以不同种类及剂量的药物。在各观察时点,动物处死前心脏抽血测定TC、TG、HDL-C、LDL-C等指标;术后3天及实验结束时心脏取血,测定5 min内血小板最大聚集率（mPAGR）。结果 （1）对AS兔血脂水平的影响：D组血脂水平与N组比较无明显变化（P>0.05）;动物喂食高脂饲料3天后TC、LDL-C即明显升高,A、B、C组与N组比较差异均有统计学意义（P＜0.05,P＜0.01）;实验结束时,与C组比较,G、E组TC、LDL-C均明显降低,G、E、F各组均能降低LDL-C/HDL-C比值,尤以G组明显（P＜0.01）;G组尚有升高HDL-C的趋势,E组变化不明显。G组可明显降低致动脉粥样硬化指数（AI,TC/HDL-C）,与C、E组比较,差异有统计学意义（P＜0.05）。（2）对血小板聚集的影响：内皮损伤后3天A、B、C组及D组mPAGR均明显升高,与N组比较差异均有统计学意义(P＜0.01);G、E、F各组均明显降低术后3天mPAGR,与C组比较,G组差异有统计学意义（P＜0.05）。G、E、F各组均可降低术后6周mPAGR,与C组比较有统计学意义（P＜005,P＜0.01）,以G组作用更为显著。结论 芎芍胶囊可降低兔动脉粥样硬化模型TC、LDL-C水平及动脉粥样硬化指数AI,还可抑制该模型的早期及术后6周血小板集聚,这些可能是其抗AS的机制之一。     

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.     

化痰祛瘀汤对动脉粥样硬化兔血管内皮功能的影响

[目的]观察化痰祛瘀汤治疗性用药对动脉粥样硬化家兔血管内皮功能的影响,探讨化痰祛瘀汤抗动脉粥样硬化的作用及可能机制。[方法]健康雄性新西兰白兔24只,随机分为三组,即正常对照组(普通饲料)、高脂模型组(普通饲料+1%胆固醇及5%猪油乳剂)、中药治疗组(普通饲料+1%胆固醇及5%猪油乳剂+化痰祛瘀汤2.0g·kg~(-1)·d~(-1)),每组8只。在实验的不同阶段,观察各组家兔血清hs-CRP、一氧化氮改变。[结果]实验12周末,高脂模型组、中药治疗组血清hs-CRP水平明显高于正常治疗组,NO明显低于正常治疗组(P值均<0.05);实验18周末,中药治疗组血清hs-CRP水平较高脂模型组显著降低,而血清NO较高脂模型组显著升高(P值均<0.05)。病理结果显示:中药治疗组主动脉粥样硬化病变及血管内皮功能损伤明显轻于高脂模型组。[结论]化痰祛瘀汤具有降低动脉粥样硬化兔血清hs-CRP及提高血清NO的水平,其作用机制可能与改善内皮细胞功能有关,从而达到抗动脉粥样硬化的作用。     

Inhibitory effects of Keishi-bukuryo-gan on free radical induced lysis of rat red blood cells

Keishi-bukuryo-gan (KBG) prevents the progression of atherosclerosis in cholesterol-fed rabbits by its antioxidative effect. The present study was to test our hypothesis that ingestion of KBG would protect red blood cell (RBC) membranes from free radical induced oxidation if polyphenolic antioxidants in KBG could be absorbed and circulated in the blood. When incubated with a RBC suspension, KBG and four of five herb medicines constituting KBG provided strong protection for RBC membranes against haemolysis induced by 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was dose dependent at concentrations of 100-1000 microg/mL. Furthermore, the ingestion of 200 mg of KBG was associated with a significant decrease in susceptibility of RBC to haemolysis in rats.     

Protective effect of flaxseed oil on renal injury in hyperlipidaemic rats: the effect of flaxseed oil on hyperlipidaemia

This study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia.     

参七黄稳斑胶囊合用辛伐他汀对家兔动脉粥样硬化斑块的影响

目的探讨参七黄稳斑胶囊单用及合用辛伐他汀对家兔动脉粥样硬化（As）斑块的影响。方法将45只家兔随机分为正常对照组（A组）、不稳定斑块对照组（B组）、参七黄稳斑胶囊治疗组（C组）、辛伐他汀治疗组（D组）、参七黄稳斑胶囊和辛伐他汀合用治疗组（E组）。A组用普通饲料,其他组用高胆固醇饲料喂养;12周末造模成功后,如前喂养,C、D、E组分别给予不同药物干预。24周末在腹主动脉注射药物触发斑块破裂,2周后检测各组血清中血管细胞粘附分子-1（VCAM-1）、细胞间粘附分子-1（ICAM-1）和超敏C反应蛋白（hs-CRP）的水平;测定斑块面积、内膜厚度、中膜厚度、纤维帽厚度。结果与B组相比,C、D、E组血清中VCAM-1、ICAM-1、hs—CRP的水平及斑块面积、内膜厚度明显降低,纤维帽明显增厚（P〈0．01）;其中C组优于D组（P〈0．05）,E组优于C组（P〈0．01）。结论参七黄稳斑胶囊有较好的稳定斑块的作用,与辛伐他汀有协同作用。     

NO-1886对食饵性高糖高脂兔脂代谢的影响

目的　观察NO - 1886对食饵性肥胖兔模型血糖、血脂和体质量的影响。方法　将新西兰兔随机分为 4组 ,每组 12只。A组喂普通饲料 ;B组先喂普通饲料 4周 ,然后在饲料中按 1.0 %的比例添加NO - 1886喂养 2 4周 ;C组喂高糖高脂饲料 (含 10 %的猪油、37%的蔗糖加普通饲料 ) ;D组先喂高糖高脂饲料 4周 ,然后在高糖高脂饲料中按1%的比例加NO - 1886喂养 2 4周。于实验 0 ,4 ,8,13,18,2 3,2 8周采血测血清HDL -C ,TG和FFAs及血清葡萄糖 ;实验期末 ,所有动物放血处死 ,分离腹部脂肪称质量。结果　喂养 2 8周后 ,D组血糖、TG和FFAs均明显低于C组 ,HDL -C明显高于C组 ,腹部脂肪明显少于C组 ,均有显著性差异 (P均 <0 .0 5 )。结论　NO - 1886具有降糖、降脂、减轻体质量的作用 ,可抑制腹部脂肪蓄积 ,预防肥胖。     

银杏叶提取物对高脂胆固醇喂饲家兔血管神经酰胺含量和泡沫细胞凋亡的影响

目的：观察预防性应用银杏叶提取物对家兔实验性动脉粥样硬化的形成、血管壁神经酰胺量和泡沫细胞凋亡的影响，探讨银杏叶提取物抗AS的作用及可能机制。方法：将24只新西兰家兔随机分为3组：正常对照组、高胆固醇组、银杏叶提取物组。分别给予普通饲料(正常对照组)和高胆固醇饮食(其它2组)喂养；银杏叶提取物组另预防性给予银杏叶提出物；实验结束后，运用图象分析法测定主动脉内膜脂质斑块面积百分比；用高效薄层层析扫描分析血管组织神经酰胺的变化；用Tunel法检测血管组织泡沫细胞的凋亡指数。结果：银杏叶提取物可明显缩小主动脉内膜脂质斑块面积，降低动脉组织神经酰胺浓度，减少血管壁泡沫细胞凋亡的数量。结论：银杏叶提取物具有较好的抗AS作用，神经酰胺与动脉粥样硬化形成和泡沫细胞凋亡有关。     

宁心痛颗粒干预模型兔动脉粥样硬化易损斑块机制研究

目的:观察宁心痛颗粒对动脉粥样(AS)易损斑块的稳定作用,探讨宁心痛颗粒稳定易损斑块的机制。方法:采用球囊损伤腹主动脉加高脂饲料喂养结合转染p53基因、中国斑点蝰蛇毒和组胺触发建立兔AS易损斑块模型,分别予宁心痛颗粒、血脂康胶囊干预,以普通病理及免疫组化观察斑块形态及NF-κB、MCP-1、MMP1的局部表达;采用Western blot技术检测NF-κB、MCP-1、MMP1水平,进行对比分析。结果:宁心痛颗粒与血脂康胶囊均能够增加纤维帽厚度及纤维帽厚度/IMT比值,降低IMT(P<0.05),两药物作用相当。免疫组化染色结果显示易损斑块模型组AS斑块处均有NF-κB、MCP-1、MMP1的局部表达,表达强度较空白组明显增强(P<0.05),宁心痛颗粒高剂量与血脂康胶囊均能够降低NF-κB、MCP-1、MMP1的表达水平(P<0.05),宁心痛颗粒高剂量与血脂康胶囊作用相当。Western blot检测模型组斑块局部NF-κB、MCP-1、MMP1蛋白水平明显增高(P<0.05),宁心痛颗粒与血脂康胶囊均能够降低NF-κB、MCP-1、MMP1蛋白水平,血脂康胶囊组NF-κB、MMP1水平略低于宁心痛颗粒高剂量组,宁心痛颗粒高剂量组NF-κB、MMP1水平低于宁心痛颗粒常规剂量组(P<0.05)。结论:宁心痛颗粒能够通过抑制炎症反应,从而达到稳定AS易损斑块的目的。     

脂汰清颗粒对实验性动脉粥样硬化兔主动脉弓超微结构的影响

目的：探讨脂汰清颗粒对实验性动脉粥样硬化兔主动脉弓超微结构的影响。方法：将新西兰兔随机选取10只作空白对照组,喂普通饲料;其余按高脂饲料配方1饲喂6周,制成高脂血症模型,再随机分为模型组、脂汰清治疗组、辛伐他汀对照组、山楂精降脂片对照组。从第7周开始,正常组喂全价营养饲料,余组改喂高脂饲料配方2。同时,脂汰清组及两对照组分别给相应溶化药物,空白组和模型组给等量生理盐水,灌胃,连续11周后检测总胆固醇（CHO）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、载脂蛋白AI（apo AI）、载脂蛋白B（apo B）,扫描电镜下观察主动脉弓组织内膜超微结构的病理变化。结果：脂汰清组可显著降低CHO、LDL-C、ApoB（P〈0.05,P〈0.01）,升高HDL-C（P〈0.05）,抑制、修复血管内皮细胞超微结构损伤。结论：脂汰清颗粒有较好的调节血脂代谢、抑制动脉粥样硬化斑块形成的作用。     

心脑血脉宁对家兔动脉粥样硬化易损斑块模型MMP-2、TIMP-2表达的影响

[目的]探讨心脑血脉宁对家兔动脉粥样硬化易损斑块模型基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响。[方法]通过喂养高脂饲料和主动脉球囊内皮拉伤术复制动脉粥样硬化易损斑块模型,实验分为模型组,假手术组,心脑血脉宁组,历时15周。处死后,取腹主动脉行苏木精-伊红(HE)染色,观察镜下病变,计数斑块破裂数,免疫组化方法检测MMP-2、TIMP-2蛋白含量。[结果]1)HE观察:假手术组镜下形态结构完整,模型组斑块中心可见大量脂核,斑块表面覆盖纤维帽,在斑块肩部可见残存泡沫细胞和大炎细胞浸润。心脑血脉宁组介于两者之间。2)免疫组化结果:与假手术组相比,模型组MMP-2、TIMP-2蛋白含量明显升高,差异有显著性(P0.01);心脑血脉宁组MMP-2与模型组比较表达降低,差异有显著性(P0.01),而TIMP-2含量与模型组相比有降低趋势,但无统计学差异(P0.05);心脑血脉宁组能够有效降低两者比值,与模型组相比差异有显著性(P0.01)。[结论]心脑血脉宁干预家兔动脉粥样硬化易损斑块模型,能减少斑块破裂,其机制可能与降低斑块MMP-2含量以及调节MMP-2与TIMP-2比值有关。     

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??OBJECTIVE To investigate the correlation of blood concentration and drug dose and reducing lipid efficacy of tectorigenin in atherosclerosis rabbits. METHODS Forty-eight Japanese white rabbits were randomly divided into six groups, the normal control group, model group, high-, middle-and low-dose (50, 25, 12.5 mg??kg^-1??d^-1) tectorigenin groups and atorvastatin (5 mg??kg^-1??d^-1) group. The normal control group was fed with routine forage, and the other groups were fed with high fat forage for the establishment of atherosclerosis model. After 8 weeks, tectorigenin blood concentration was detected by HPLC. After 12 weeks, blood lipids were detected with automatic biochemical analyzer. We sheared the thoracic and abdominal aorta to observe the formation of atherosclerotic plaque and make pathologic examination. RESULTS Steady-state blood concentration increased with the increase of drug dose, there was a positive relationship (r=0.969 1) between them, but not the same proportion. After treatment, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol (LDL-C ) levels were decreased and high density lipoprotein cholesterol (HDL-C) were increased in the tectorigenin each dose group, but the effect was weaker than atorvastatin group. CONCLUSION Tectorigenin has obvious effect on reducing blood lipid and anti-atherosclerosis in rabbits, and it is related to the blood concentration and the drug dose.     

CRP与在体兔动脉粥样硬化相关性的研究及桑葚提取物的影响

目的探讨炎症敏感指标C－反应蛋白（CRP）与实验性高脂饮食新西兰兔动脉粥样硬化的相关性及桑葚提取物对其的影响。方法36只新西兰免随机分为6组,正常对照组给予普通饮食;模型组给予高脂饮食;血脂康阳性对照组予高脂饮食加血脂康;预防用药组将桑葚提取液与高脂饲料喂养新西兰兔,该组又分为低剂量组（1g／kg）、中卉j量组（5g／kg）,高剂量组（10g／kg）。于用药即刻、2周、4周、6周、8周末时测定血清CRP的含量,8周末杀兔取胸主动脉,测定动脉内膜的厚度确定动脉粥样硬化的程度。分析CRP与动脉内膜厚度的相关性。结果从实验第2周起与正常对照组相比模型组兔血清CRP含量显著升高（P〈0．01）,桑葚3个剂量组与模型组相比CRP含量显著降低（P〈0．01）;与正常对照组比较模型组动脉内膜显著增厚（P〈0．01）;与模型组相比桑葚3个剂量组动脉内膜的厚度显著减小（P〈0．01）;CRP浓度与动脉内膜厚度呈显著正相关（r=0．56,P〈0．01）。结论CRP与动脉粥样粥样硬化的形成呈正相关。桑葚提取物可有效降低高脂饮食新西兰免血清CRP的水平,从而抑制和延缓兔动脉粥样硬化的形成。     

赤芍川芎有效部位对兔动脉粥样硬化基质金属蛋白酶的影响

目的 观察芎芍胶囊（XSC,赤芍川芎有效部位）对兔动脉粥样硬化模型中基质金属蛋白酶(matrix metalloproteinases, MMPs)表达水平的影响。     

补肾宁心方对去卵巢兔动脉粥样硬化的保护作用

目的 研究补肾宁心方对去卵巢兔动脉粥样硬化形成的影响。方法 26只3月龄新西兰雌兔随机分为正常组、假手术组、对照组(卵巢切除)、中药组(卵巢切除并灌以补肾宁心方),除正常组外均于手术2周后给予高脂饮食,中药组同时灌胃给补肾宁心方中药,连续3个月。各组于第12周末测定血脂(TC、TG、LDL-C和HDL-C)以及一氧化氮(NO)水平;取主动脉行组织形态学观察以及在光镜和扫描电子显微镜下行病理学检查,利用图像分析仪计算动脉粥样硬化斑块内膜面积比和内膜中膜厚度比、面积比。结果 12周末除正常组外,各组动物血脂测定结果比较,差异无显著性。与对照组比较,中药组血清NO水平明显升高,主动脉硬化斑块面积与动脉内膜比值,内膜中膜厚度比、面积比均明显降低,主动脉病理变化减轻。结论 补肾宁心方可抑制去势雌兔动脉粥样硬化形成,对血管内皮细胞具有保护作用。     

稳消颗粒对兔实验性动脉粥样硬化血清FIB和CRP表达的影响

目的观察稳消颗粒对兔实验性动脉粥样硬化血清C反应蛋白（CRP）和纤维蛋白原（FIB）表达的影响。方法健康新西兰大白兔36只,随机分为空白组（正常饮食）9只和造模组（高脂饮食）27只。造模成功后将造模组再随机分为稳消颗粒组、辛伐他汀组、模型对照组。停用高脂饲料改用标准饲料并根据体重比折算临床剂量给予相应的药物治疗8周。分别于实验前与实验后经耳缘静脉采血,检测CRP和FIB水平。结果与空白组相比,稳消颗粒组、辛伐他汀组和模型对照组的CRP、FIB水平显著增高（P〈0.05）;稳消颗粒组、辛伐他汀组CRP、FIB明显低于模型对照组（P〈0.05）,但稳消颗粒组、辛伐他汀组之间比较无统计学意义（P〉0.05）。结论稳消颗粒可降低CRP、FIB水平,有利于AS斑块稳定。     

益寿调脂片抗高脂血症及动脉粥样硬化的实验研究

观察益寿调脂片对兔高脂血症，动脉粥样硬化模型中脂质人才主动脉内膜斑块形成的影响。方法：将３２只家兔随机分为４组，益寿调脂片组喂高脂饲料加益寿调脂片１．５９ｇ．ｋｇ＾－１．ｄ＾－１，绞股蓝总甙片组喂高脂饲料绞股蓝总甙片２２．５４ｍｇ．ｋｇ＾－１．ｄ＾－１，高脂组喂高脂饲料，正常组喂普通饲料，６周后测定有关生化指标并进行病理形态学检查。     

芎芍胶囊对动脉粥样硬化兔血管平滑肌细胞增殖的影响

目的 研究芎芍胶囊对实验性兔动脉粥样硬化（AS）血管平滑肌细胞（VSMC）增殖的影响,并探讨其可能的机制。     

Effect of Amirkabiria odorastissima mozaffarian on the development and progression of fatty streaks in hypercholesterolemic rabbits

New studies have introduced atherosclerosis as an inflammatory disease. Different factors affect the development of inflammation that can be linked to free radicals, hypertention, diabetes mellitus, genetic changes, hypercholesterolemia and some of the microorganisms. Using anti-inflammatory drugs can be useful in preventing atherosclerosis. Finding drugs from natural sources and without side-effects can be useful. Amirkabiria odoratissima (umbelliferae) is from Iranian fl ora and is used traditionally as an anti-inflammatory drug. This study was designed to assess the effects of this plant on the development and progression of fatty streaks. Male rabbits were fed: (a) rabbit chow; (b) 1% cholesterol diet; (c) cholesterol diet supplemented with the plant; (d) normal diet supplemented with the plant. After 12 weeks, the animals were sacrificed and the aorta, right and left branches of coronary arteries were dissected and histologically processed. Before and after the end of the study, biochemical factors were measured. The amounts of cholesterol, LDL, HDL, triglyceride and fasting blood sugar (FBS) were determined by enzymatic methods, quantitative CRP was determined by turbidimetric methods, malondialdehyde (MDA) and antioxidant capacity were determined by speceterophotometric methods. The results indicate that there is a significant difference between the groups supplemented with herbal medicine and others (p < 0.05) in the mean grade of fatty streak of right and left coronary artery and aorta. At the end of the 12-week period cholesterol, LDL and CRP were significantly reduced in the groups which received herbal medicine (p < 0.05). The data suggests that Amirkabiria odoratissima Mozaffarian has beneficial effects to prevent development of fatty streak; however, further studies are needed to understand the mechanisms whereby this plant exerts its anti-atherosclerotic effects.