α-ZAL、GST和17β E_2对去势食饵性大鼠HHCY所致血管内皮损伤的保护作用  

Comparison between α-zearalanol,genistein and 17β-estrodial on hyperhomocysteinemia-induced endothelial dysfunction in ovariectomized rats

作　　者：洪霓[1] 段金虹[1] 张彦东[1] 吴云清[1] 甄攀攀[2] 蒋东桥[2] 戴顺龄[1] 王雯[2] 

机构地区：[1]中国医学科学院基础医学研究所中国协和医科大学基础医学院,北京100005 [2]首都医科大学病理生理学教研室,北京100069

出　　处：《中国药理学通报》2009年第7期891-894,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30700293);北京市自然科学基金资助项目(No7082013);北京市教委科技发展计划资助项目(NoKM200910025003)

摘　　要：目的复制去势(OVX)大鼠高同型半胱氨酸血症(HHCY)模型,比较植物雌激素α-玉米赤霉醇(α-ZAL)、染料木素(GST)和17β雌二醇(17βE2)对血管内皮的保护作用。方法实验分为6组:①正常对照组(Control);②假手术+2.5%蛋氨酸组(Sham);③切除卵巢+2.5%蛋氨酸组(OVX);④OVX+2.5%蛋氨酸+α-ZAL组(OVX+α-ZAL);⑤OVX+2.5%蛋氨酸+GST组(OVX+GST);⑥OVX+2.5%蛋氨酸+17βE2组(OVX+17βE2)。α-ZAL、GST和17βE2分别隔日肌注250μg/0.25ml,共12wk。双抗夹心法测定HCY和ET-1浓度,RT-PCR法检测主动脉组织ET-1 mRNA表达;主动脉作病理制片。结果血浆HCY含量(μmol.L-1):Sham与Con组比较明显升高,P<0.05;OVX组与Sham组相比明显升高,P<0.05;而OVX+α-ZAL、OVX+GST和OVX+17βE2组与OVX组相比均降低,P<0.01。血浆ET-1(ng.L-1)含量:OVX组与Sham组相比较ET-1升高,P<0.01,而OVX+α-ZAL、OVX+GST和OVX+17βE2组与OVX组相比均降低,P<0.01。主动脉组织ET-1 mRNA的表达:OVX组与Sham组相比较升高,P<0.05,而OVX+α-ZAL、OVX+GST和OVX+17βE2组与OVX组相比均降低,P<0.05,其它各组ET-1 mRNA表达均无变化。病理:OVX组血管内皮明显损伤,Sham组、α-ZAL、GST和17βE2组血管内膜大致正常,内皮细胞基本完整,未见明显的炎性细胞浸润。结论α-ZAL、GST和17βE2均能通过降低HCY含量和减少ET-1分泌、表达而保护血管内皮,三者的内皮保护作用相似。Aim To compare the effects of phytoestrogen α-zearalanol （α-ZAL） , genistein （GST） and endogenious estrogen 17β-estrodial （17βE2） on hyperho- mocysteinemia （HHCY）-induced endothelial dysfunction in ovariectomized rats. Methods Sixty female Wistar rats were divided into six groups：Control;Sham ＋ 2. 5 % methionine in diet （Sham） ; ovariectomized ＋2.5% methionine （OVX） ; ovariectomized ＋ 2.5% methionine ＋ α-ZAL （OVX ＋ α-ZAL） ; ovariectomized ＋2.5% methionine ＋ GST（ OVX ＋ GST） ; ovariectomized ＋ 2.5% methionine ＋ 17βE2 （ OVX ＋ 17βE2）. α-ZAL,GST and 17βE2（250 μg） were im every other day for 12 weeks. The plasma concentration of homocysteine （HCY） and endothelin-1 （ ET-1 ） were detected using enzymatic immunoassay. The endothelin-1 mRNA level was detected using RT-PCR. Results After being fed with high methionine diet for 12 weeks, the plasma HCY level, ET-1 level and aorta ET-1 mRNA were increased significantly in OVX rats, and the endothelial injury of aorta was also very significant under microscope. Supplement with α-ZAL, GST and 17βE2 could not only attenuate the increased plasma HCY and ET-1 level and aorta ET-1 mRNA, but also attenuate the endothelial pathologic injury in ovariectomized HHCY rats, there was no significant difference between these three drugs. Conclusion α-ZAL, GST and 17βE2 may protect vascular endothelium in ovari- ectomized HHCY rats through decreasing HCY production and ET-1 secretion, whose protective effects are similar.

关 键 词：Α-玉米赤霉醇 染料木素 17Β雌二醇 高同型半胱氨酸血症 内皮素 

分 类 号：R282.71[医药卫生—中药学] R322.123[医药卫生—中医学]