CAJ | 학술논문

目的研究高同型半胱氨酸(HHcy)、非对称性二甲基精氨酸(ADMA)对大鼠脑血管结构的影响,并探讨普罗布考、叶酸及维生素B12对其干预的效果. 方法 70只雄性SD大鼠随机分为7组:对照组、HHcy模型组、普罗布考(低剂量、中剂量、高剂量)组、叶酸+维生素B12(两药联合)组、叶酸+维生素B12+普罗布考(3药联合)组.正常对照组给予普通饲料喂养予蒸馏水灌胃;其他6组给予2％蛋氨酸饲料喂养,并分别给予蒸馏水、不同剂量普罗布考(340、510、680 mg·kg1·d-1)、叶酸+维生素B12、叶酸+维生素B12+普罗布考灌胃.于实验开始、第8及12周末采用高压液相荧光检测法测定大鼠血浆Hcy、ADMA水平;于第12周末采用电镜观察各组大鼠脑血管结构的改变. 结果高蛋氨酸饮食8周后,正常对照组Hcy水平为(7.1±1.4) μmol/L,低于HHCY模型组(60.4±11.9) μmol/L; HHCY模型组ADMA为(1.3±0.4)μmol/L,高于正常对照组(0.4±0.1)μmol/L.12周末,血浆Hcy、ADMA水平低剂量组为(49.9±11.4)μmol/L和(1.0±0.2)μmol/L、中剂量组(46.8±10.9) μmol/L和(0.9±0.1)μmol/L、高剂量组(44.3±11.4)μmol/L和(0.9±0.1)μmol/L、两药联合组(16.3±4.9)μmol/L和(0.7±0.2) μmol/L,较HHCY模型组(69.5±11.4)μmol/L和(1.6±0.5) μmol/L降低,但高于正常对照组(6.7±1.3)μmol/L和(0.5±0.1)μmol/L,差异有统计学意义(P＜0.05).3药联合组Hcy、ADMA水平分别为(8.9±1.9) μmol/L和(0.6±0.2) μmol/L,较HHCY模型组下降(P＜0.05),但与正常对照组比较差异无统计学意义(P＞0.05).相关分析显示血浆Hcy与ADMA呈正相关(P＜0.05).电镜下HHCY模型组大鼠脑动脉及大脑皮质结构均可见损伤,应用普罗布考、叶酸及维生素B12干预后大鼠脑血管结构损伤较HHCY模型组减轻,3药联合组减轻更明显. 结论 HHcy、ADMA能够对大鼠脑血管结构造成损伤;普罗布考、叶酸及维生素B12可通过降低Hcy、ADMA水平,减轻脑血管的损伤,且3种药物联合效果更显著. 目的研究高同型半胱氨痠(HHcy)、非對稱性二甲基精氨痠(ADMA)對大鼠腦血管結構的影響,併探討普囉佈攷、葉痠及維生素B12對其榦預的效果. 方法 70隻雄性SD大鼠隨機分為7組:對照組、HHcy模型組、普囉佈攷(低劑量、中劑量、高劑量)組、葉痠+維生素B12(兩藥聯閤)組、葉痠+維生素B12+普囉佈攷(3藥聯閤)組.正常對照組給予普通飼料餵養予蒸餾水灌胃;其他6組給予2％蛋氨痠飼料餵養,併分彆給予蒸餾水、不同劑量普囉佈攷(340、510、680 mg·kg1·d-1)、葉痠+維生素B12、葉痠+維生素B12+普囉佈攷灌胃.于實驗開始、第8及12週末採用高壓液相熒光檢測法測定大鼠血漿Hcy、ADMA水平;于第12週末採用電鏡觀察各組大鼠腦血管結構的改變. 結果高蛋氨痠飲食8週後,正常對照組Hcy水平為(7.1±1.4) μmol/L,低于HHCY模型組(60.4±11.9) μmol/L; HHCY模型組ADMA為(1.3±0.4)μmol/L,高于正常對照組(0.4±0.1)μmol/L.12週末,血漿Hcy、ADMA水平低劑量組為(49.9±11.4)μmol/L和(1.0±0.2)μmol/L、中劑量組(46.8±10.9) μmol/L和(0.9±0.1)μmol/L、高劑量組(44.3±11.4)μmol/L和(0.9±0.1)μmol/L、兩藥聯閤組(16.3±4.9)μmol/L和(0.7±0.2) μmol/L,較HHCY模型組(69.5±11.4)μmol/L和(1.6±0.5) μmol/L降低,但高于正常對照組(6.7±1.3)μmol/L和(0.5±0.1)μmol/L,差異有統計學意義(P＜0.05).3藥聯閤組Hcy、ADMA水平分彆為(8.9±1.9) μmol/L和(0.6±0.2) μmol/L,較HHCY模型組下降(P＜0.05),但與正常對照組比較差異無統計學意義(P＞0.05).相關分析顯示血漿Hcy與ADMA呈正相關(P＜0.05).電鏡下HHCY模型組大鼠腦動脈及大腦皮質結構均可見損傷,應用普囉佈攷、葉痠及維生素B12榦預後大鼠腦血管結構損傷較HHCY模型組減輕,3藥聯閤組減輕更明顯. 結論 HHcy、ADMA能夠對大鼠腦血管結構造成損傷;普囉佈攷、葉痠及維生素B12可通過降低Hcy、ADMA水平,減輕腦血管的損傷,且3種藥物聯閤效果更顯著.
목적 연구고동형반광안산(HHcy)、비대칭성이갑기정안산(ADMA)대대서뇌혈관결구적영향,병탐토보라포고、협산급유생소B12대기간예적효과. 방법 70지웅성SD대서수궤분위7조:대조조、HHcy모형조、보라포고(저제량、중제량、고제량)조、협산+유생소B12(량약연합)조、협산+유생소B12+보라포고(3약연합)조.정상대조조급여보통사료위양여증류수관위;기타6조급여2％단안산사료위양,병분별급여증류수、불동제량보라포고(340、510、680 mg·kg1·d-1)、협산+유생소B12、협산+유생소B12+보라포고관위.우실험개시、제8급12주말채용고압액상형광검측법측정대서혈장Hcy、ADMA수평;우제12주말채용전경관찰각조대서뇌혈관결구적개변. 결과 고단안산음식8주후,정상대조조Hcy수평위(7.1±1.4) μmol/L,저우HHCY모형조(60.4±11.9) μmol/L; HHCY모형조ADMA위(1.3±0.4)μmol/L,고우정상대조조(0.4±0.1)μmol/L.12주말,혈장Hcy、ADMA수평저제량조위(49.9±11.4)μmol/L화(1.0±0.2)μmol/L、중제량조(46.8±10.9) μmol/L화(0.9±0.1)μmol/L、고제량조(44.3±11.4)μmol/L화(0.9±0.1)μmol/L、량약연합조(16.3±4.9)μmol/L화(0.7±0.2) μmol/L,교HHCY모형조(69.5±11.4)μmol/L화(1.6±0.5) μmol/L강저,단고우정상대조조(6.7±1.3)μmol/L화(0.5±0.1)μmol/L,차이유통계학의의(P＜0.05).3약연합조Hcy、ADMA수평분별위(8.9±1.9) μmol/L화(0.6±0.2) μmol/L,교HHCY모형조하강(P＜0.05),단여정상대조조비교차이무통계학의의(P＞0.05).상관분석현시혈장Hcy여ADMA정정상관(P＜0.05).전경하HHCY모형조대서뇌동맥급대뇌피질결구균가견손상,응용보라포고、협산급유생소B12간예후대서뇌혈관결구손상교HHCY모형조감경,3약연합조감경경명현. 결론 HHcy、ADMA능구대대서뇌혈관결구조성손상;보라포고、협산급유생소B12가통과강저Hcy、ADMA수평,감경뇌혈관적손상,차3충약물연합효과경현저.
Objective To study the damage of hyperhomocysteinemia (HHcy) and asymmetric dimethylarginine (ADMA) on the structure of rats cerebral vessels,and to explore the treatment effect of probucol,folic acid and vitamin B12.Methods Totally,70 male Sprague-Dawley(SD) rats were randomly divided into seven groups:normal control (A),HHcy model (B),low-dose-probucol (C),middle-dose-probucol (D),high-dose-probucol (E),folic-acid plus vitamin B12 (F),folic-acid plus vitamin B12 plus probucol(G)group.Group A was fed plain feedstuff and water.Other groups were fed homomethionin feedstuff and water,probucol (340,510,680 mg· kg-1 · d-1),folic acid and vitamin B12,folic acid plus vitamin B12 plus probucol respectively.The plasma concentrations of homocysteine(Hcy) and ADMA were assayed by high-performance liquid chromatography method (HPLC) at the beginning,and at the end of 8 and 12 weeks.The analysis of rats cerebral vessels was performed with electron microscope at the end of 12 weeks.Results (1) After adding high concentrations of methionine feedstuff for 8 weeks,the levels of Hcy in group B (60.4±11.9) μmol/L were significantly raised compared with group A(7.1±1.4) μmol/L.Meanwhile,ADMA levels in group B(1.3±0.4)μmol/L were higher than group A(0.4±0.1) μmol/L.At the end of 12 week,the levels of Hcy and ADMA were lower in groups C[(49.9±11.4)μmol/L,(1.0±0.2)μmol/L],D [(46.8± 10.9)μmol/L,(0.9±0.1)μmol/L],E[(44.3±11.4)μmol/L,(0.9±0.1)μmol/L],F [(16.3 ± 4.9)μmol/L,(0.7 ± 0.2)μmol/L] compared with group B [(69.5 ± 11.4)μmol/L,(1.6 ±0.5)μmol/L],but higher than group A[(6.7±1.3)μmol/L,(0.5±0.1)μmol/L].The levels of Hcy and ADMA in group G[(8.9±1.9) μmol/L,(0.6±0.2) μmol/L]were also lower than those in group B (P＜0.05],but they did not show statistically significant differences compared with group A(P＞0.05).(2) According to correlative analysis,Hcy levels were positively correlated with ADMA levels (P＜0.05).(3) On electron microscope,we observed that the cerebral artery and cerebral cortex of group B were seriously damaged.After the intervention with probucol,folic acid and vitamin B12,the structure of rats cerebral vessels were improved in group C,D,E,F and G as compared with group B,and group G were especially improved more obviously.Conclusions The HHcy and ADMA could damage the structure of rats cerebral vessels.Probucol,folic acid and vitamin B12 may alleviate the cerebral vascular damage by decreasing the levels of Hcy and ADMA,and the effect is more significant by the combined drug regimens of Probucol,folic acid and vitamin B12.