雌激素與運動訓練對大白鼠骨骼形態及一氧化氮合成酉每 表現之影響

The Effect of Estrogen and Exercise Training on Nitric Oxide Isoforms expression and Bone mechanical Properties in Ovariectomized Rats

洪暐(Wei Hung)

指導教授 ： 方進隆 ； 李士元 ； 徐佳福

國立臺灣師範大學/運動與休閒學院/體育學系/博士(2000年)

摘要

前人研究成果提出，一氧化氮合成脢確實存在與骨骼組織中三種最主要的細胞：骨細胞、造骨細胞與破骨細胞，而不論是離體細胞培養實驗或是活體骨骼組織機械應力刺激實驗均發現，骨骼組織細胞在受到應力刺激後會產生多量的一氧化氮，而一氧化氮也被證實與破骨細胞、造骨細胞之間的相互調控有密不可分的關係，而運動訓練過程中對於骨骼組織產生的影響是否就是經由一氧化氮合成脢作為傳導的媒介？而雌激素與運動訓練對保護骨骼組織產生的加成性效果是否也與一氧化氮合成脢有關，此二疑點及為本研究之主要目的，本研究結合運動訓練與雌激素補充治療，並以一氧化氮合成脢抑制劑交互使用，以期探討一氧化氮合成脢在整個訊息傳導過程中扮演的角色與定位。八十隻十二週齡之大白鼠隨機分派成八組，分別給予運動訓練、雌激素補充以及一氧化氮合成脢抑制劑或合併運動訓練與雌激素補充、運動訓練以及一氧化氮合成脢抑制劑、雌激素補充合併一氧化氮合成脢抑制劑之處理，經過十二週原地跑步機之運動訓練後分別進行股骨頸耐壓能力、股骨頸斷裂部位X光吸光值、一氧化氮合成脢表現量之分析。研究結果：（1） 合併運動訓練與雌激素補充治療之大鼠骨骼組織中內皮型一氧化氮合成脢與誘發型一氧化氮合成脢表現量高於單獨使用雌激素治療或運動訓練之大鼠。（2） 使用一氧化氮合成脢抑制劑卻直阻斷運動訓練保護骨質流失的效果，但對雌激素補充治療的阻斷效果較不明顯。本研究提出下列兩點結論：
（1） 一氧化氮合成脢確實在運動訓練影響骨骼組織的訊息傳導過程專扮演不可或缺的關鍵角色。
（2） 雌激素補充治療與運動訓練合併使用產生的加成性效應可能尚有其他代償機轉，並不一定完全經由一氧化氮合成脢轉介。

關鍵字

一氧化氮合成脢 ； 雌激素 ； 運動訓練

並列摘要

The modulator between osteoblast and osteoclast used to be as inflammatory cytokines such as interlukin-6, TNF and IGF. In passed years, spotlight of bone modulator had turned to be nitric oxide, a short-lived free radical that is generated by the NO synthase group of enzymes which syntheses NO by combine molecular oxygen with the terminal guanidino nitrogen of the amino acid L-arginine. Due to the small molecular size, NO can pass through most kind of membrance easily and act on guanidine cyclase. By changing conformation of guanidine cyclase and altering cGMP level of cytosol, NO affects cell proliferation or activity such as osteoclast. Three isoforms of nitric oxide synthase has been identified , however , only two of them were expressed in bone tissue : endothelial form (eNOS) and induce form (iNOS). Recent study had indicated that osteoblast and osteocyte mainly express endothelial form of NOS under normal conditions, while osteoclast express not only eNOS but also iNOS , even though the later is much weakly.
Recent study had confirmed the additive effect of exercise training and ERT. Nitric oxide synthase might play an important role in this process. In this study, we assume that nitric oxide synthase is the key enzyme which mediate signal transduction of estrogen and mechanical strain. Eighty Spraque-Dawley rats were randomly assign to eight groups, which treated with exercise training, Estrogen replacement therapy(ERT), nitric oxide synthase inhibitor(NOS inhibitor), Exercxuse and ERT, Exercise and NOS inhibitor or ERT and NOS inhibitor, respectively. The data of mechanical and biochemical test wee collected and analysed by SPSS9.0, results were followed:
(1) Both ERT and exercise training enhance nitric oxide synthase expression, combine two method shows significant additive effect.
(2) Nitric oxide synthase inhibitor suppresses mechanically induced bone formation and reduces maximal loading force of femur neck

並列關鍵字

Nitric oxide synthase ； exercise ； Estrogen replacement therapy

參考文獻

黃滄海。（民90）不同強度的耐力性游泳運動對大鼠骨骼發展的影響。國立台灣師範大學體育研究所。未發表之博士論文。

張豐麟。（民90）持續性與間歇式動訓練對大鼠骨骼發展的影響。國立台灣師範大學體育研究所。未發表之碩士論文。

Naoyuki Takahashi,Takuhiko Akatsu,Nobuyuki Udagawa, Takashisa Sasaki, Akria Yamaguchi, Jane M. Moseley, T. John Martin and Tatsuo Suda (1988) Osteoblastic Cells Are Involved in Osteolast Formation. Endocrinology, 2600-2602

Robert L.Jika,Giao Hangoc,Giuseppe Girasole, Giovanni Passeri, Daniel C.Williams, John S. Abrams, Brendan Boyce, Hal Broxmeyer,Stavros C.Manolagas (1992) Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6. Science, 257 88-91

William R. Phipps,Margaret C. Martini, Johnna W. Lampe, Joanne L. Slavin, and Mindy S. Kurzer (1993) Effect of flax Seed Ingestion on the Menstrual Cycle. Journal of Clinical Endocrinology and Metabolism, 77, 1215-1219