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类固醇激素对雌性膀胱形态及血管内皮生长因子表达的影响

Effects of steroid hormones on morphology and vascular endothelial growth factor expression in female bladder.

作者信息

Yu Yanlan, Shen Zhoujun, Zhou Xielai, Chen Shanwen

机构信息

Department of Urology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

出版信息

Urology. 2009 Jun;73(6):1210-7. doi: 10.1016/j.urology.2008.10.050. Epub 2009 Apr 18.

DOI:10.1016/j.urology.2008.10.050
PMID:19376567
Abstract

OBJECTIVES

To investigate the roles of steroid hormones, including estrogen, progesterone, and testosterone, in the morphology and vascularization of the female bladder.

METHODS

A total of 70 adult, female Sprague-Dawley rats were divided into 7 groups: group 1, sham; group 2, ovariectomized rats without treatment; group 3, low-dose estradiol; group 4, high-dose estradiol; group 5, progesterone; group 6, estradiol combined with progesterone; and group 7, testosterone. All were given for 4 weeks. The serum steroid hormone levels were determined by radioimmunoassay. The total weight and thickness of the bladder were measured. Morphologic changes were observed under light and electron microscopy. The expression of vascular endothelial growth factor (VEGF) in the bladder was evaluated by immmohistochemistry and Western blotting.

RESULTS

The ovariectomized rats had a thinner bladder wall compared with the sham group (0.97 +/- 0.11 mm vs 1.10 +/- 0.10 mm, P < .05) and widened spaces between the detrusor muscle fascicles with collagen deposit. Estrogen reversed these changes, and testosterone increased the thickness of the bladder wall to 1.26 +/- 0.12 mm (P < .05). VEGF staining was mainly located in the urothelium and endothelial cells, with weak staining in the smooth muscles. VEGF was almost absent in the urothelium after ovariectomy. In the estrogen- and androgen-treated groups, although the expression of VEGF was significantly greater than that in the nontreated ovariectomized group, it was still lower than normal.

CONCLUSIONS

Our findings suggest the importance of steroid hormones in maintaining the integrity of the bladder structure and regulating the expression of VEGF in the female urinary tract. Both estrogen and androgen can reverse the bladder muscle atrophy induced by ovariectomy. However, the decline in VEGF expression in the bladder cannot be fully recovered with either estrogen or androgen replacement.

摘要

目的

研究雌激素、孕激素和睾酮等甾体激素在雌性膀胱形态及血管形成中的作用。

方法

将70只成年雌性Sprague-Dawley大鼠分为7组:第1组为假手术组;第2组为未治疗的去卵巢大鼠;第3组为低剂量雌二醇组;第4组为高剂量雌二醇组;第5组为孕激素组;第6组为雌二醇联合孕激素组;第7组为睾酮组。所有处理均持续4周。采用放射免疫分析法测定血清甾体激素水平。测量膀胱的总重量和厚度。在光镜和电镜下观察形态学变化。采用免疫组织化学和蛋白质印迹法评估膀胱中血管内皮生长因子(VEGF)的表达。

结果

与假手术组相比,去卵巢大鼠的膀胱壁更薄(0.97±0.11mm对1.10±0.10mm,P<0.05),逼尿肌束间间隙增宽并有胶原沉积。雌激素可逆转这些变化,睾酮则使膀胱壁厚度增加至1.26±0.12mm(P<0.05)。VEGF染色主要位于尿路上皮和内皮细胞,平滑肌染色较弱。去卵巢后尿路上皮中几乎没有VEGF。在雌激素和雄激素治疗组中,尽管VEGF的表达明显高于未治疗的去卵巢组,但仍低于正常水平。

结论

我们的研究结果表明甾体激素在维持膀胱结构完整性和调节雌性尿路VEGF表达方面具有重要作用。雌激素和雄激素均可逆转去卵巢诱导的膀胱肌肉萎缩。然而,雌激素或雄激素替代均不能完全恢复膀胱中VEGF表达的下降。

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