摘要
背景:内皮细胞发生结构损伤和功能障碍的主要特征为内皮细胞活性降低或释放的一氧化氮减少,内皮缩血管肽产生增加。目的:探讨黄芪多糖抗动脉粥样硬化内皮细胞损伤的作用,并以卡托普利做标准对照。设计:随机对照观察。单位:湖北中医学院生理教研室,武汉大学医学院病理生理教研室,广东省荷塘医院外科,武汉大学人民医院内分泌科。材料:实验于2001-07/2002-11在湖北中医学院机能实验室和武汉大学医学院病理生理教研室完成。选择由武汉大学医学院实验动物中心提供的健康国产雄性家兔40只,体质量2.4～3.0kg,随机分为空白组、模型对照组、黄芪多糖组、卡托普利组(标准对照),10只/组。黄芪多糖从山西产黄芪根中提取,制成注射用粉剂,用前以生理盐水新鲜配制。方法:空白组给予正常颗料饲料,其余3组从实验第1天起给予高脂饲料(80%基础饲料中加入15%蛋黄粉、0.5%胆固醇和5%猪油),牛血清1mL/kg从耳缘静脉注射1次,用高脂饲料加免疫损伤建立兔动脉粥样硬化内皮细胞损伤模型。黄芪多糖组每天腹腔注射黄芪多糖500mg/kg;卡托普利组给予5mg/kg卡托普利,相当于临床剂量的5倍;空白组、模型对照组给予等体积的生理盐水4mL/kg,共给药50d。末次给药后24h,从上腔静脉取血后处死动物,腹主动脉形态学变化光镜下观察,并测定家兔血清中总胆固醇、三酰甘油、一氧化氮、内皮缩血管肽、超氧化物歧化酶、丙二醛、总抗氧化活力的变化。主要观察指标:①腹主动脉形态学变化。②血清中各项相关指标变化检测。结果:40只家兔全部纳入实验。①与模型对照组比较,黄芪多糖组和卡托普利组血清中总胆固醇、三酰甘油含量明显降低[(9.33±1.13),(6.60±0.61),(7.09±0.74)mmol/L,P<0.05;(3.05±0.44),(1.26±0.16),(2.17±0.46)mmol/L,P<0.01,P<0.05];且丙二醛和内皮缩血管肽含量也明显降低[(9.98±1.11),(7.10±0.68),(9.46±1.27)μmol/L,P<0.01;(741.90±34.98),(632.62±26.95),(600.74±32.59)ng/L,P<0.01]。②与模型对照组比较,黄芪多糖组和卡托普利组血清中一氧化氮、超氧化物歧化酶含量显著提高[(11.04±1.68),(19.96±6.05),(18.35±3.52)μmol/L,P<0.01,P<0.05;(159.32±5.26),(207.54±16.98),(197.59±28.41)NU/mL,P<0.01,P<0.05];同时总抗氧化活力升高[(23.8±3.5),(34.7±5.6),(30.7±6.8)%,P<0.01,P<0.05]。③黄芪多糖组无论是血清中总胆固醇、三酰甘油及丙二醛含量的降低或一氧化氮、超氧化物歧化酶及总抗氧化活力的升高均优于卡托普利组(P<0.01)。④腹主动脉形态学变化观察结果,可见空白组腹主动脉内膜表面光滑,内皮细胞连续,细胞间隙较小,内皮细胞无水肿,形态正常;模型对照组腹主动脉内膜增厚、隆起,血管内皮细胞可见部分脱落,细胞间隙增宽,内皮细胞有水肿。中膜层明显增厚,平滑肌细胞增生明显,且迁入内皮下,可见泡沫细胞;黄芪多糖组腹主动脉内膜表面基本光滑,细胞连接较紧密,平滑肌细胞增生不活跃,泡沫细胞少见;卡托普利组腹主动脉内膜表面基本光滑,内皮细胞无明显脱落,无平滑肌细胞迁入,平滑肌细胞形态基本正常,排列规则。结论:黄芪多糖可明显降低血清中总胆固醇、三酰甘油、丙二醛和内皮缩血管肽的含量,从而减轻内皮缩血管肽对血管的损伤作用;同时升高一氧化氮、超氧化物歧化酶及总抗氧化活力,应用黄芪多糖家兔光镜下可见腹主动脉内膜表面基本光滑,内皮细胞形态基本完好,提示其具有较好的对抗氧化损伤和保护血管内皮细胞的功能。
BACKGROUND: The structural and functional impairment of endothelium cells were mainly presented by lowered endothelium activity, reduced nitrogen monoxide production, as well as increased endothelium vasoconstrictor peptide (EVCP). OBJECTIVE: To study the protective role of astragalus polysaccharide on atherosclerosis induced by endothelium cell injury, which was compared with that of Captopril. DESIGN: Randomly controlled observation. SETTING: Department of Physiology, Hubei College of Traditional Chinese Medicine; Department of Pathophysiology, Medical College of Wuhan University; Department of Surgery, Hetang Hospital of Guangdong Province; Department of Endocrinopathic Sciences, Renmin Hospital, Wuhan University. MATERIALS: The study was carried out at the Organic Function Laboratory of Hubei College of Traditional Chinese Medicine and the Pathophysiological Department of Wuhan Medical University from July 2001 to December 2002. Forty healthy male rabbits provided by the experimental animal center of Wuhan medical university, weighed of 2.4-3.0 kg, were randomly divided into blank group, model control group, astragalus polysaccharide group and captopril group with 10 rabbits in each group. Astragalus polysaccharide was extracted from Shanxi produced astragalus root and made into injection powder that should be freshly composed with physical saline before usage. METHODS: Rabbits in blank group were raised with granular feed, while rabbits in other three groups were given hyperlipid feed (80% basal feed mixed with 15% yolk powder, 0.5% cholesterin and 5% lard), in addition with venous injection of bovine serum by 1 mL/kg once, atherosclerosis induced endothelium injury model was established on rabbit by hyperlipid feed combined with immune injury. Rabbits in astragalus polysaccharide group received intraperitoneal injection of polysaccharide of 500 mg/kg once a day; which replaced by 5 mg/kg captopril in captopril group that equals to 5 times clinical dosage; While rabbits in blank group and model control group were given the same volume physical saline of 4 mL/kg for totally 50 days. Blood were collected from SVC 24 after the last medication and then rabbits were put to death, the morphological changes of abdominal aorta were observed under optical microscope, meanwhile the changes of serum total cholesterol, triglycerides, nitrogen monoxide, EVCP, superoxide dismutase, malonaldehyde and total antioxidation activity were examined. MAIN OUTCOME MEASURES: ① Morphological changes of abdominal aorta. ② Changes of serum parameters. RESULTS: All 40 rabbits complete the experiment without loss. ① In contrast with model control group group, the total serum total cholesterol and triglycerides in astragalus polysaccharide group and captopril group obviously decreased [(9.33±1.13), (6.60±0.61), (7.09±0.74) mmol/L, P < 0.05;(3.05±0.44), (1.26±0.16), (2.17±0.46) mmol/L, P < 0.01, P< 0.05], malonaldehyde and EVCP markedly decreased [(9.98±1.11), (7.10±0.68), (9.46±1.27) μmol/L, P < 0.01; (741.90±34.98), (632.62±26.95), (600.74±32.59) ng/L, P < 0.01]. ② Comparing to model control group group, the serum nitrogen monoxide and superoxide dismutase were obviously increased in astragalus polysaccharide group and captopril group [(11.04±1.68), (19.96±6.05), (18.35±3.52) μmol/L, P < 0.01, P < 0.05; (159.32±5.26), (207.54±16.98), (197.59±28.41) NU/mL, P < 0.01, P < 0.05], the total antioxidation activity also increased [(23.8±3.5), (34.7±5.6), (30.7±6.8)%, P < 0.01, P < 0.05]. ③ Either the decrement of serum triglycerides, total cholesterol and malonaldehyde or the increment of nitrogen monoxide, superoxide dismutase and total antioxidation activity in astragalus polysaccharide group was greater than captopril group (P < 0.01). ④ Morphological changes of abdominal aorta: The aorta intima was smooth and endothelium cells were continuous with small intervals between cells in blank control group,endothelium cells presented normal configuration without edema; while intima in model control group became thick and upheaved, part of endothelium cells detached with widened intervals. The media became thickened with leiomyocyte displaying hyperplasic and infiltering into endothelium, foaming cells could also be observed; the aorta intima was smooth and endothelium was closely connected in astragalus polysaccharide group, the hyperplasia of leiomyocyte was not active and foaming cells seldom observed; while in captopril group, the aorta intima was smooth without obvious detachment of endothelium cells and infiltration of leiomyocyte, leiomyocytes were normal and ranked orderly. CONCLUSION: Astragalus polysaccharide could markedly eliminate serum triglycerides, total cholesterol, malonaldehyde and EVCP, thereby alleviate vascular impairment induced by EVCP, meanwhile markedly increased serum nitrogen monoxide, superoxide dismutase and total antioxidation activity, the intima surface of abdominal aorta could be smooth due to the administration of AP, endothelium configuration would be basically complete, implying that it has better antioxidation property and protective role for endothelium cells.
出处
《中国临床康复》
CSCD
北大核心
2005年第23期238-240,共3页
Chinese Journal of Clinical Rehabilitation
基金
国家自然科学基金(No 30370673)~~
