CAJ | 학술논문

目的探讨早期不同剂量雌激素替代治疗(ERT)对去卵巢高脂血症雌兔主动脉内皮衰老的影响及可能机制.方法 28只健康新西兰雌性白兔随机分为4组(每组7只):假手术组行假手术;去卵巢组行双侧卵巢切除;小剂量ERT组行双侧卵巢切除加小剂量ERT(苯甲酸雌二醇200μg,隔日肌肉注射1次);大剂量ERT组行双侧卵巢切除加大ERT剂量(苯甲酸雌二醇1000 μg,隔日肌肉注射1次).各组兔于术后1周开始给予高脂饲料喂养,小剂量ERT组和大剂量ERT组同时给予ERT.分别于术前、高脂喂食4周及12周后抽取耳中央动脉血,测定血清雌二醇、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白一胆固醇(HDL-C)及非对称性二甲基精氨酸(ADMA)水平.实验结束时,分离兔主动脉行组织病理学分析并计算衰老血管内皮和动脉粥样硬化斑块面积.结果 (1)12周后去卵巢组血清TC及LDL-C高于其他组(P<0.01),而TG及HDL-C水平低于其他3组(P<0.01);小剂量和大剂量ERT组TC及LDL-C低于假手术组(P<0.05),但TG及HDL-C与假手术组比较,差异无统计学意义(均P>0.05).(2)高脂喂食12周后各组兔血清ADMA水平均明显增高,小剂量和大剂量ERT组低于假手术组(P<0.05).(3)直线相关分析显示,主动脉粥样斑块面积与衰老内皮面积呈正相关(r=0.962,P<0.01),两者均与血清TC、LDL-C和ADMA浓度呈正相关(r值分别为0.812、0.824、0.755、0.797、0.749、0.727,P<0.01),与血清雌二醇呈显著负相关(r=-0.762和-0.743,P<0.01).结论早期ERT可以改善血脂代谢、降低ADMA水平、减轻血管内皮衰老及动脉粥样硬化斑块形成,雌激素延缓内皮衰老的作用可能与改善血脂代谢、降低ADMA水平有关.
목적 탐토조기불동제량자격소체대치료(ERT)대거란소고지혈증자토주동맥내피쇠로적영향급가능궤제.방법 28지건강신서란자성백토수궤분위4조(매조7지):가수술조행가수술;거란소조행쌍측란소절제;소제량ERT조행쌍측란소절제가소제량ERT(분갑산자이순200μg,격일기육주사1차);대제량ERT조행쌍측란소절제가대ERT제량(분갑산자이순1000 μg,격일기육주사1차).각조토우술후1주개시급여고지사료위양,소제량ERT조화대제량ERT조동시급여ERT.분별우술전、고지위식4주급12주후추취이중앙동맥혈,측정혈청자이순、총담고순(TC)、삼선감유(TG)、저밀도지단백-담고순(LDL-C)、고밀도지단백일담고순(HDL-C)급비대칭성이갑기정안산(ADMA)수평.실험결속시,분리토주동맥행조직병이학분석병계산쇠로혈관내피화동맥죽양경화반괴면적.결과 (1)12주후거란소조혈청TC급LDL-C고우기타조(P<0.01),이TG급HDL-C수평저우기타3조(P<0.01);소제량화대제량ERT조TC급LDL-C저우가수술조(P<0.05),단TG급HDL-C여가수술조비교,차이무통계학의의(균P>0.05).(2)고지위식12주후각조토혈청ADMA수평균명현증고,소제량화대제량ERT조저우가수술조(P<0.05).(3)직선상관분석현시,주동맥죽양반괴면적여쇠로내피면적정정상관(r=0.962,P<0.01),량자균여혈청TC、LDL-C화ADMA농도정정상관(r치분별위0.812、0.824、0.755、0.797、0.749、0.727,P<0.01),여혈청자이순정현저부상관(r=-0.762화-0.743,P<0.01).결론 조기ERT가이개선혈지대사、강저ADMA수평、감경혈관내피쇠로급동맥죽양경화반괴형성,자격소연완내피쇠로적작용가능여개선혈지대사、강저ADMA수평유관.
Objective To investigate the effects of early estrogen replacement therapy(ERT) with different doses on aortic endothelial senescence and its possible mechanism. Methods Twenty- eight healthy New Zealand white female rabbits were randomized into four groups: group A(n=7), in sham operation;group B(n=7), ovariectomized;group C(n=7), ovariectomized and in low-dose ERT(estradiol benzoate 200 μg,im, QOD) ;and group D(n=7), ovariectomized and in high-dose ERT (estradiol benzoate 1000 μg,im,QOD). All rabbits were fed with high fat diet and the rabbits in group C and group D were given ERT from the 7th day after the operation. Blood samples taken via ear central artery before the operation and after the high fat diet for 4 and 12 weeks were used to determine the concentrations of serum estradiol(E2), total cholesterol(TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), trigtyceride (TG) and asymmetric dimethylarginine(ADMA). After 12 weeks, the aorta was separated for histopathologic analysis and the areas of senescent endothelium and atherosclerotic plaque were calculated.Results (1)After ovariectomized, the concentration of serum estradiol(E2) was significantly lower in group B than in other groups (all P<0.05). Twelve weeks later, the level of E2in was higher group D than in group A and C(both P<0. 05), but there was no significant difference between group C and group A (P< 0. 05). (2)After the high-fat diet for 4 and 12 weeks, there was a notable increase of TC, LDL-C, TG and HDL-C levels in rabbits of each group(all P<0. 01). After 12 weeks, the levels of TC and LDL- C were remarkably higher in group B than in other groups(all P<0. 01), however, the levels of TG and HDL-C were lower in group B than in other groups(all P<0. 01). The concentrations of TC and LDL-C in group C and group D were lower than those in group A (all P<0.01), but the differences of the levels of TG and HDL-C in group C and group D were not significant in comparison with group A (all P>0. 05). There were no significant differences in the lipid levels between group C and D (all P> 0. 05). (3)After 12-week high fat diet, there were a striking increases of serum ADMA level in all four groups (all P>0. 05). The level of ADMA was higher in group B than in other groups (P< 0. 05) andlower in group C and D than that in group A (both P<0. 05). There was no significant difference between group C and D (P<0. 05). (4)12 weeks later, the areas of senescent endothelium and atherosclerotic plaque in group B were significantly larger than those in other groups (all P< 0. 01), and the areas were smaller in group C and D than those in group A (all P<0. 01), there was no significant difference between group C and group D(both P>0.05). (5)Linear correlation analysis showed that there was an obvious positive correlation between the areas of senescent endothelium and atherosclerotic plaque(r=0. 962, P<0. 01), and both of them were positively correlated with the levels of serum AMDA (r=0. 812,0. 824,0. 755,0. 797,0. 749,0. 727), TC (r=0. 812,0. 824) and LDL-C(r=0. 755,0. 797) (all P<0. 01) and negatively correlated with the concentration of serum E2 (r=-0. 762,-0. 743, both P<0. 01).Conclusions Early ERT can improve serum lipid metabolism, reduce ADMA level, inhibit vascular endothelial senescence and attenuate atherogenesis. The delaying effect of estrogen on endothelial senescence may be due to its improving lipid metabolism and lowering ADMA level.