在卵巢切除動物模式中調節性蛋白對過動性膀胱的影響

卵巢切除（Ovx）動物模式誘導膀胱排尿功能障礙已建立模仿像更年期婦女尿失現象。本研究主要探討經卵巢切除後一氧化氮(NO)前驅物L-精氨酸(L-arginine)對膀胱功能的影響。二十八隻雌兔分成七組。實驗組 1至6施行卵巢切除手術。其中，第一，二組接受卵巢切除手術但沒有給與 L-精氨酸飲食。實驗組第3，4，5和6組給予高劑量L -精氨酸的飲食和分別依序於卵巢切除後第1，3，7和14日內犧牲實驗兔子，而實驗組第7組作為無任何處理的對照組。進而探討在各種不同刺激的反應下，L-精氨酸對於膀胱收縮功能的影響。此外，利用西方點墨法技術來研究探討L -精氨酸對Rho-激酶(Rho-kinase, ROK), 蛋白激酶C抑制劑(protein kinase C potentiated inhibitor, CPI-17), caldesmon (CaD) 和calponin (CaP),的影響及表達。結果長期卵巢切除的動物膀胱表現不正常收縮排尿且降低排尿順應性。同時顯著增加膀胱的粘膜和平滑肌層細胞凋亡，並促使膀胱間質纖維化。另外在卵巢切除動物的膀胱之氧化性傷害標誌物(Oxidative stress markers),硝基(nitrotyrosine)和羰基蛋白(protein carbonylation)含量顯著增加。因此，卵巢切除動物膀胱平滑肌明顯降低各種形式的刺激收縮反應。進一步地飼餵L-精氨酸於實驗兔子，結果在第1天後膀胱平滑肌的收縮反應顯著提高，但第14天收縮反應降低到正常水平。同時在卵巢切除動物的膀胱組織中兩個亞型CAD及CAP和CPI-17的表達增加，另外L-精氨酸治療引起ROK表達減少但CAP是在卵巢切除後早期幾天卻過度表達，2週後返回到正常水平。卵巢切除後膀胱細胞凋亡增加，氧化性的損害和誘導過動性膀胱(OAB)的症狀。卵巢切除雖降低膀胱收縮力，給予L-精氨酸治療後具有潛在的逆轉去卵巢切除後引起膀胱收縮反應下降的功能障礙，特別是在手術後的早期幾天。

關鍵字

卵巢切除；調節性蛋白；過動性膀胱； L-精氨酸

並列摘要

A rat model of ovariectomy (Ovx)-induced voiding dysfunction has been established which mimicked the urge incontinence in menopausal women. The present study was designed to investigate the effect of nitric oxide (NO) precursor, L-arginine, on bladder function following Ovx. Twenty-eight female rabbits were separated into seven groups. Groups 1 to 6 underwent Ovx surgery. Among them, groups 1 and 2 received Ovx without treating with L-arginine. Groups 3, 4, 5 and 6 were given high L-arginine diet and were sacrificed 1, 3, 7 and 14 days after Ovx, respectively. Group 7 was served as the control group. The effects of L-arginine on the contractile of bladder tissues were determined in response to various stimulations. In addition, L-arginine effects on the expression of Rho-kinase (ROK), protein kinase C potentiated inhibitor (CPI-17), caldesmon (CaD) and calponin (CaP) were studied by immunoblotting. As a result, long term Ovx significantly increased non-voiding contractions and decreased bladder compliance. Ovx also significantly increased apoptotic cells both in mucosa and in smooth muscle layers and prompted bladder interstitial fibrosis. Additionally, oxidative stress markers, nitrotyrosine and protein carbonylation levels significantly increased in the Ovx group. Therefore, Ovx significantly decreases contractile response to all forms of stimulation. For furture investigation, feeding rabbits L-arginine significantly increases contractile response at 1 day following Ovx but the response decreases to the control level by 14 days. Moreover, Ovx increases the expressions of both isoforms of CaD, CaP and CPI-17, L-arginine treatment induces ROK underexpression while CaP is overexpressed in the early few days of Ovx but returns to the control level at 2 weeks after Ovx. Ovx increased apoptosis, oxidative stress damages in the bladder and induced OAB symptoms. Ovx appreciably reduces bladder contractility, however treatment with L-arginine has potential in the reversal of Ovx-induced bladder dysfunction, decreases in bladder contractile response, especially in the early few days following Ovx.

並列關鍵字

ovariectomy ； regulatory protein ； overactive bladder ； L-arginine

參考文獻

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在卵巢切除動物模式中調節性蛋白對過動性膀胱的影響

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