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骨髓间充质干细胞治疗大鼠双侧盆神经挤压所致排尿功能障碍。

Bone marrow mesenchymal stem cells therapy on bilateral pelvic nerve crush-induced voiding dysfunction in rats.

机构信息

Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.

出版信息

Int Urogynecol J. 2022 Sep;33(9):2485-2492. doi: 10.1007/s00192-022-05099-4. Epub 2022 Apr 22.

DOI:10.1007/s00192-022-05099-4
PMID:35451617
Abstract

INTRODUCTION AND HYPOTHESIS

Neurogenic voiding dysfunction can be induced after radical pelvic surgery and severely affects patients' quality of life. This study aims to investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on neurogenic voiding dysfunction in male rats and explore the underlying mechanisms.

METHODS

Thirty 4-week-old male Sprague-Dawley rats were randomly divided into three groups: (1) sham-operated (sham, n = 10), (2) intrabladder wall injection of phosphate buffer solution (PBS) after bilateral pelvic nerve crush (BPNC+PBS, n = 10), and (3) intrabladder wall injection of BMSCs after bilateral pelvic nerve crush (BPNC+BMSCs, n = 10). Four weeks postoperatively, functional and morphological examinations were performed.

RESULTS

Compared to the sham group, BPNC rats manifested significant augmentation in the frequency of non-voiding contractions and postvoid residual and bladder capacity, and they had decreases in intravesical pressure and voiding efficiency. However, they were markedly improved after BMSC injection. Masson's trichrome staining showed that the ratio of collagen area in bladder wall tissue significantly increased in the BPNC+PBS group but was reduced following BMSC injection. BPNC increased the protein expression of TGF-β1, Smad2/3, and collagen I/III but decreased the expression of α-SMA. BMSC injection stimulated higher expression levels of α-SMA and lower expression levels of the other target proteins. The expression levels of vesicular acetylcholine transporters were reduced at 4 weeks post-BPNC, whereas injection of BMSCs boosted the expression quantity.

CONCLUSIONS

BMSC therapy suppressed detrusor fibrosis, improved intravesical pressure and voiding efficiency, and partially restored voiding function in male rats after BPNC.

摘要

介绍和假设

盆腔根治性手术后可引起神经性排尿功能障碍,严重影响患者的生活质量。本研究旨在探讨骨髓间充质干细胞(BMSCs)对雄性大鼠神经性排尿功能障碍的影响,并探讨其潜在机制。

方法

30 只 4 周龄雄性 Sprague-Dawley 大鼠随机分为三组:(1)假手术组(sham,n=10),(2)双侧盆神经挤压后膀胱壁内注射磷酸盐缓冲液(BPNC+PBS,n=10),(3)双侧盆神经挤压后膀胱壁内注射 BMSCs(BPNC+BMSCs,n=10)。术后 4 周进行功能和形态学检查。

结果

与 sham 组相比,BPNC 组大鼠非排尿收缩频率、残余尿量和膀胱容量明显增加,膀胱内压和排尿效率降低;但 BMSC 注射后明显改善。Masson 三色染色显示,BPNC+PBS 组膀胱壁组织胶原面积比显著增加,而 BMSC 注射后则减少。BPNC 增加了 TGF-β1、Smad2/3 和胶原 I/III 的蛋白表达,但降低了 α-SMA 的表达。BMSC 注射刺激了更高水平的 α-SMA 和更低水平的其他靶蛋白。BPNC 后 4 周,囊泡乙酰胆碱转运体的表达减少,而 BMSCs 注射增加了其表达量。

结论

BMSC 治疗抑制逼尿肌纤维化,改善膀胱内压和排尿效率,部分恢复雄性大鼠 BPNC 后的排尿功能。

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