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2.4～3.0 kg,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1 mL/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500 mg/kg;卡托普利组给予5m/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4 mL/kg,共给药50 d.末次给药后24 h,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.
揹景:內皮細胞髮生結構損傷和功能障礙的主要特徵為內皮細胞活性降低或釋放的一氧化氮減少,內皮縮血管肽產生增加.目的:探討黃芪多糖抗動脈粥樣硬化內皮細胞損傷的作用,併以卡託普利做標準對照.設計:隨機對照觀察.單位:湖北中醫學院生理教研室,武漢大學醫學院病理生理教研室,廣東省荷塘醫院外科,武漢大學人民醫院內分泌科.材料:實驗于2001-07/2002-11在湖北中醫學院機能實驗室和武漢大學醫學院病理生理教研室完成.選擇由武漢大學醫學院實驗動物中心提供的健康國產雄性傢兔40隻,體質量2.4～3.0 kg,隨機分為空白組、模型對照組、黃芪多糖組、卡託普利組(標準對照),10隻/組.黃芪多糖從山西產黃芪根中提取,製成註射用粉劑,用前以生理鹽水新鮮配製.方法:空白組給予正常顆料飼料,其餘3組從實驗第1天起給予高脂飼料(80%基礎飼料中加入15%蛋黃粉、0.5%膽固醇和5%豬油),牛血清1 mL/kg從耳緣靜脈註射1次,用高脂飼料加免疫損傷建立兔動脈粥樣硬化內皮細胞損傷模型.黃芪多糖組每天腹腔註射黃芪多糖500 mg/kg;卡託普利組給予5m/kg卡託普利,相噹于臨床劑量的5倍;空白組、模型對照組給予等體積的生理鹽水4 mL/kg,共給藥50 d.末次給藥後24 h,從上腔靜脈取血後處死動物,腹主動脈形態學變化光鏡下觀察,併測定傢兔血清中總膽固醇、三酰甘油、一氧化氮、內皮縮血管肽、超氧化物歧化酶、丙二醛、總抗氧化活力的變化.主要觀察指標:①腹主動脈形態學變化.②血清中各項相關指標變化檢測.結果:40隻傢兔全部納入實驗.①與模型對照組比較,黃芪多糖組和卡託普利組血清中總膽固醇、三酰甘油含量明顯降低[(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];且丙二醛和內皮縮血管肽含量也明顯降低[(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與模型對照組比較,黃芪多糖組和卡託普利組血清中一氧化氮、超氧化物歧化酶含量顯著提高[(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];同時總抗氧化活力升高[(23.8±3.5),(34.7±5.6),(30.7±6.8)%,P＜0.01,P＜0.05].③黃芪多糖組無論是血清中總膽固醇、三酰甘油及丙二醛含量的降低或一氧化氮、超氧化物歧化酶及總抗氧化活力的升高均優于卡託普利組(P＜0.01).④腹主動脈形態學變化觀察結果,可見空白組腹主動脈內膜錶麵光滑,內皮細胞連續,細胞間隙較小,內皮細胞無水腫,形態正常;模型對照組腹主動脈內膜增厚、隆起,血管內皮細胞可見部分脫落,細胞間隙增寬,內皮細胞有水腫.中膜層明顯增厚,平滑肌細胞增生明顯,且遷入內皮下,可見泡沫細胞;黃芪多糖組腹主動脈內膜錶麵基本光滑,細胞連接較緊密,平滑肌細胞增生不活躍,泡沫細胞少見;卡託普利組腹主動脈內膜錶麵基本光滑,內皮細胞無明顯脫落,無平滑肌細胞遷入,平滑肌細胞形態基本正常,排列規則.結論:黃芪多糖可明顯降低血清中總膽固醇、三酰甘油、丙二醛和內皮縮血管肽的含量,從而減輕內皮縮血管肽對血管的損傷作用;同時升高一氧化氮、超氧化物歧化酶及總抗氧化活力,應用黃芪多糖傢兔光鏡下可見腹主動脈內膜錶麵基本光滑,內皮細胞形態基本完好,提示其具有較好的對抗氧化損傷和保護血管內皮細胞的功能.
배경:내피세포발생결구손상화공능장애적주요특정위내피세포활성강저혹석방적일양화담감소,내피축혈관태산생증가.목적:탐토황기다당항동맥죽양경화내피세포손상적작용,병이잡탁보리주표준대조.설계:수궤대조관찰.단위:호북중의학원생리교연실,무한대학의학원병리생리교연실,광동성하당의원외과,무한대학인민의원내분비과.재료:실험우2001-07/2002-11재호북중의학원궤능실험실화무한대학의학원병리생리교연실완성.선택유무한대학의학원실험동물중심제공적건강국산웅성가토40지,체질량2.4～3.0 kg,수궤분위공백조、모형대조조、황기다당조、잡탁보리조(표준대조),10지/조.황기다당종산서산황기근중제취,제성주사용분제,용전이생리염수신선배제.방법:공백조급여정상과료사료,기여3조종실험제1천기급여고지사료(80%기출사료중가입15%단황분、0.5%담고순화5%저유),우혈청1 mL/kg종이연정맥주사1차,용고지사료가면역손상건립토동맥죽양경화내피세포손상모형.황기다당조매천복강주사황기다당500 mg/kg;잡탁보리조급여5m/kg잡탁보리,상당우림상제량적5배;공백조、모형대조조급여등체적적생리염수4 mL/kg,공급약50 d.말차급약후24 h,종상강정맥취혈후처사동물,복주동맥형태학변화광경하관찰,병측정가토혈청중총담고순、삼선감유、일양화담、내피축혈관태、초양화물기화매、병이철、총항양화활력적변화.주요관찰지표:①복주동맥형태학변화.②혈청중각항상관지표변화검측.결과:40지가토전부납입실험.①여모형대조조비교,황기다당조화잡탁보리조혈청중총담고순、삼선감유함량명현강저[(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];차병이철화내피축혈관태함량야명현강저[(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].②여모형대조조비교,황기다당조화잡탁보리조혈청중일양화담、초양화물기화매함량현저제고[(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];동시총항양화활력승고[(23.8±3.5),(34.7±5.6),(30.7±6.8)%,P＜0.01,P＜0.05].③황기다당조무론시혈청중총담고순、삼선감유급병이철함량적강저혹일양화담、초양화물기화매급총항양화활력적승고균우우잡탁보리조(P＜0.01).④복주동맥형태학변화관찰결과,가견공백조복주동맥내막표면광활,내피세포련속,세포간극교소,내피세포무수종,형태정상;모형대조조복주동맥내막증후、륭기,혈관내피세포가견부분탈락,세포간극증관,내피세포유수종.중막층명현증후,평활기세포증생명현,차천입내피하,가견포말세포;황기다당조복주동맥내막표면기본광활,세포련접교긴밀,평활기세포증생불활약,포말세포소견;잡탁보리조복주동맥내막표면기본광활,내피세포무명현탈락,무평활기세포천입,평활기세포형태기본정상,배렬규칙.결론:황기다당가명현강저혈청중총담고순、삼선감유、병이철화내피축혈관태적함량,종이감경내피축혈관태대혈관적손상작용;동시승고일양화담、초양화물기화매급총항양화활력,응용황기다당가토광경하가견복주동맥내막표면기본광활,내피세포형태기본완호,제시기구유교호적대항양화손상화보호혈관내피세포적공능.
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 eudothelium 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 changesof 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 ＜ 0.0l, 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 endothelinm 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.
