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兔部分膀胱出口梗阻模型中注射入逼尿肌的核心蛋白聚糖的组织病理学和药效学作用

The histopathological and pharmacodynamic effects of intradetrusor decorin injected in a rabbit partial bladder outlet obstruction model.

作者信息

Kaya Engin, Kibar Yusuf, Yılmaz Sercan, Ebiloglu Turgay, Ozcan Ayhan, Seyrek Melik, Yıldız Oguzhan, Ulusoy Kemal Gokhan

机构信息

Gulhane Military Medical Academy, Ankara, Turkey.

出版信息

Int Urol Nephrol. 2017 Apr;49(4):607-614. doi: 10.1007/s11255-017-1518-x. Epub 2017 Jan 30.

DOI:10.1007/s11255-017-1518-x
PMID:28138904
Abstract

PURPOSE

To evaluate whether or not the bladder function can be protected by supporting the detrusor with decorin levels during the fibrotic process.

METHODS

Forty-two male rabbits were divided into three main groups, partial bladder outlet obstruction (pBOO) group, pBOO + intradetrusor decorin-injected (IDI) group and control group. Both pBOO and pBOO + IDI groups were divided into three subgroups according to the killing schedule. Histopathological, immunohistochemical and pharmacodynamics studies were performed for the evaluation of fibrotic process and tissue characteristics.

RESULTS

Histopathological evaluation revealed statistically significant high fibrosis levels for both pBOO and pBOO + IDI groups when compared with control. Strikingly the antifibrotic effect of decorin was significant on 2nd, 4th and 8th week and increased as time passed. Immunohistochemical analysis was revealed high expressions of anti-TGF-β1 and decorin levels in all pBOO + IDI groups. Pharmacodynamical results were also revealed better contraction responses in favor of 2nd, 4th and 8th week groups of pBOO + IDI groups, when compared with pBOO groups. In addition, the contraction responses against the depolarizer agent KCl were increased in the three decorin-administrated groups.

CONCLUSION

Our study demonstrates the antifibrotic effects of decorin on bladder fibrosis. Strikingly, this antifibrotic effect is shown in histopathological, immunohistochemical and pharmacodynamics studies. Although further studies are warranted to make more decisive inferences regarding its clinical use, our study has the proper pride to be the first step of this time course.

摘要

目的

评估在纤维化过程中通过增加核心蛋白聚糖水平来支持逼尿肌是否能够保护膀胱功能。

方法

42只雄性兔子被分为三个主要组,即部分膀胱出口梗阻(pBOO)组、pBOO + 膀胱逼尿肌内注射核心蛋白聚糖(IDI)组和对照组。根据处死时间安排,pBOO组和pBOO + IDI组又各自分为三个亚组。进行组织病理学、免疫组织化学和药效学研究以评估纤维化过程和组织特征。

结果

组织病理学评估显示,与对照组相比,pBOO组和pBOO + IDI组的纤维化水平在统计学上显著更高。引人注目的是,核心蛋白聚糖的抗纤维化作用在第2周、第4周和第8周时显著,且随时间推移而增强。免疫组织化学分析显示,所有pBOO + IDI组中抗转化生长因子-β1和核心蛋白聚糖水平均高表达。药效学结果还显示,与pBOO组相比,pBOO + IDI组在第2周、第4周和第8周的亚组中收缩反应更好。此外,在三个给予核心蛋白聚糖的组中,对去极化剂氯化钾的收缩反应增强。

结论

我们的研究证明了核心蛋白聚糖对膀胱纤维化具有抗纤维化作用。引人注目的是,这种抗纤维化作用在组织病理学、免疫组织化学和药效学研究中均有体现。尽管需要进一步研究以对其临床应用做出更具决定性的推断,但我们的研究有理由成为这一进程的第一步。

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本文引用的文献

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Proteomic profile of an acute partial bladder outlet obstruction.急性部分膀胱出口梗阻的蛋白质组学特征
Can Urol Assoc J. 2015 Mar-Apr;9(3-4):E114-21. doi: 10.5489/cuaj.2267.
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Decorin treatment of spinal cord injury.核心蛋白聚糖对脊髓损伤的治疗作用
Neural Regen Res. 2014 Sep 15;9(18):1653-6. doi: 10.4103/1673-5374.141797.
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Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture.关节内硫酸皮肤素影响兔关节挛缩模型中纤维化基因表达谱。
Bone Joint Res. 2014 Mar 26;3(3):82-8. doi: 10.1302/2046-3758.33.2000276. Print 2014.
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Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model.动物模型中口服药物治疗部分膀胱出口梗阻后的尿动力学改善
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Differential expression of class I small leucine-rich proteoglycans in an animal model of partial bladder outlet obstruction.在部分膀胱出口梗阻动物模型中 I 类小富含亮氨酸的蛋白聚糖的差异表达。
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The histopathologic, pharmacologic and urodynamic results of mesenchymal stem cell's injection into the decompensated rabbit's bladder.间质干细胞注射至失代偿兔膀胱后的组织病理学、药理学和尿动力学结果。
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Decorin as a new treatment alternative in Peyronie's disease: preliminary results in the rat model.腱糖蛋白 I 作为一种新的治疗选择在 Peyronie 病中的应用:大鼠模型中的初步结果。
Andrologia. 2013 Apr;45(2):101-6. doi: 10.1111/j.1439-0272.2012.01318.x. Epub 2012 Jun 6.
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The effect of intravesical acetylsalicylic acid instillation on tissue prostaglandin levels after partial bladder outlet obstruction in rabbits.经尿道给予乙酰水杨酸对兔部分膀胱出口梗阻后组织前列腺素水平的影响。
Neurourol Urodyn. 2011 Nov;30(8):1646-51. doi: 10.1002/nau.21153. Epub 2011 Aug 8.
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Small leucine-rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar.小富含亮氨酸的蛋白聚糖、核心蛋白聚糖和纤调蛋白在烧伤后增生性瘢痕中减少。
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