| Abstract: | 本研究發現雌性素，對心臟確實具有保護作用。實驗中將大白鼠分為兩組，一為卵巢完整 ( sham )，另一為3週卵巢切除( OVX )，同時再將各組腹動脈結紮四天及腹動脈結紮八天或不結紮。並分別在大白鼠腹動脈結紮前四天，前一天，及結紮後三天，注射雌性素 ( 17-β-E2，100ng/kg B.W.)。同時由心臟外觀，心臟全重及左心室重與體重的比例及matrix-metalloproteases 含量，作為手術成功的指標。再進一步探討,insulin-like growth factor-1 ( IGF-1 )，insulin-like growth factor-1 receptor ( IGF-1R )和cytochrome-c-oxidase( COX vb )基因的表現差異及其相關訊息傳遞途徑，包含心肌生存途徑；PI3K-Akt，非心肌細胞增生相關途徑；MEK-ERK，及可能之病理性肥大途徑；calcineurin-NFAT3的蛋白表現量與雌性素存在與否關係，並比較內生性雌性素及外生性雌性素補充對心臟影響的差異。結果顯示，內生性雌性素，在動脈阻塞下，對心肌功能維護相當重要。且雌性素保護心肌的機轉，與促進心肌生存途徑及非心肌細胞增生途徑，及壓制病理性肥大途徑有關。而雌性素的存在與否，並直接影響動脈結紮動物心肌中IGF-，IGF- R及COX vb的基因表現。唯獨較長期八天結紮動物，明顯造成心肌病變發生，額外補充雌性素失效且內生性雌性素的缺乏更加速病徵。
In order to investigate the cardiac protective effect of 17b-estradiol(E2). Sprague-Dawley (SD) rats were ovariectomy(OVX) month before and then subjected to a complete coarctation(COX) of the abdominal aorta to induce cardiac hypertrophy. Short term 4 days and longer 8 days COX was conducted to monitoring the changes of heart size, matrix-metalloproteases (MMPs) and insulin-like growth factor-I (IGF-I), insulin-like growth factor I receptor (IGF-IR), cytochrome-c-oxidase (Cox-Vb) gene expressions, and their related signal pathways under the deficiency of estrogen, and further to examine the influence of 17b-estradiol replacement once of every three days (100ng/kg B.W.). Results showed that COX elevated the heart and left ventricular weight of ovary intake (Sham) animal on day 4, but it was attenuated by E2 replacement. Moreover, the sham animals almost overcome the hypertrophy effect by COX on day 8 after E2 replacement, but it did not restore in OVX animals, and then even went worst and more fibrosis occurred. Besides, the latent form of MMP2 that responsible for collagen turn over and heart remodeling, increased on day 4 of COX animals in both sham and OVX groups, and reversed by E2 replacement. However, the latent MMP2 pool was consumed out on day 8 of COX animals and the frequency of fibrosis was elevated. This situation only reversed in sham animals but not in OVX groups. At the mean time, the cardio-myocytes survival and non-cardiomyocytes proliferation pathways, IGFIR-PI3K-AKT and MEK-ERK1/2, activities are maintained or even more activated on day 4 COX animals between sham and OVX groups, but down-regulated observed on day 8-COX animals in OVX groups with or without E2 supplement. However, the calcineurin-NFAT3 pathway was suppressed on the heart of day 4 sham animals, which probably the reason without cardiac disorders occurred in this manner. Although the protein concentration arised on days 4 OVX and day 8 sham animals with coartation, there is no change of NFAT3 activities. Then, the calcineurin amount and NFAT3 activites the elevated of day 8 OVX animals. According to our findings, we recongized that only exogenous E2 is not enoguh to reverse the damages in heart induced by longer pressure over-loaded in the OVX animals. However, the ovary intake SD rats with sufficient endogenous E2, plus the E2 replacement did show the cardiac protective effect and reverse the cardiac disorders. Induced by abdominal aorta stenosis. The mechanism is prob-ably mediated through the upregulation of insulin-like growth factor-1 singlings and the suppression of calcineurin/NFAT3 pathway. |
