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绿茶儿茶素可降低手术绝经后大鼠模型中过动性膀胱的氧化应激。

Green tea catechins decrease oxidative stress in surgical menopause-induced overactive bladder in a rat model.

机构信息

Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

BJU Int. 2012 Sep;110(6 Pt B):E236-44. doi: 10.1111/j.1464-410X.2012.11258.x. Epub 2012 May 28.

Abstract

UNLABELLED

What's known on the subject? and What does the study add? Ovary hormone deficiency and the age-related changes in post-menopausal women are subjected to a number of urological dysfunctions, including overactive bladder syndrome. Green tea is a popular healthy drink worldwide and its extract catechin has strong anti-inflammatory and antioxidant properties. EGCG, the major type of catechin, is an antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could prevent ovariectomy-induced bladder dysfunction in a dose-related manner through its anti-oxidant, anti-fibrosis and anti-apoptosis effects.

OBJECTIVE

To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects.

MATERIALS AND METHODS

In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 µM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 µM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers.

RESULTS

Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-β, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-β and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion.

CONCLUSIONS

Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects.

摘要

目的

评估绿茶提取物表没食子儿茶素没食子酸酯(EGCG)是否可以预防卵巢切除术后逼尿肌过度活动(OAB),并研究其抗氧化、抗凋亡和抗纤维化作用。

材料和方法

总共 48 只雌性 Sprague-Dawley 大鼠被分为四组。在双侧卵巢切除术后,第一组作为卵巢切除对照组,第二组在卵巢切除手术后每天接受 1µM/kg 的 EGCG 腹腔注射,第三组接受 10µM/kg 的 EGCG 腹腔注射。第四组为未进行卵巢切除术的假手术组。在卵巢切除手术后 6 个月时处死大鼠。进行膀胱测压以测量膀胱过度活动。末端脱氧核苷酸转移酶介导的 dUTP-生物素切口末端标记(TUNEL)测定法用于评估凋亡细胞。进行 Western 免疫印迹以确定炎症标志物、凋亡相关蛋白和氧化应激标志物的表达。

结果

长期卵巢切除显著增加非排空收缩并降低膀胱顺应性。EGCG 治疗显著增加了膀胱顺应性并减少了非排空收缩。卵巢切除显著增加了膀胱中的凋亡细胞并增强了间质纤维化。卵巢切除后 caspase-3 的表达显著增加,而 Bcl-2 的表达明显减少。手术后 6 个月,TGF-β、纤维连接蛋白和 I 型胶原的表达显著增加。EGCG 治疗显著降低了 TGF-β和 I 型胶原的表达。卵巢切除组中硝基酪氨酸和蛋白质羰基化水平等氧化应激标志物显著增加。EGCG 可以以剂量依赖的方式减轻这种氧化损伤。

结论

卵巢切除增加了氧化损伤,增加了排尿频率并降低了膀胱顺应性。EGCG 可以通过抗氧化、抗纤维化和抗凋亡作用以剂量依赖的方式恢复卵巢切除引起的膀胱功能障碍。

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