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富血小板血浆注射治疗难治性复发性尿路感染后尿路上皮健康:改善细胞增殖、细胞骨架和屏障功能蛋白表达。

Urothelial health after platelet-rich plasma injection in intractable recurrent urinary tract infection: Improved cell proliferation, cytoskeleton, and barrier function protein expression.

机构信息

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Department of Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

出版信息

Low Urin Tract Symptoms. 2021 Apr;13(2):271-278. doi: 10.1111/luts.12364. Epub 2020 Nov 16.

Abstract

OBJECTIVE

This clinical study used autologous intravesical platelet-rich plasma (PRP) injections to treat patients with recurrent urinary tract infection (rUTI). Changes in urothelial proliferation, cytoskeleton, and barrier function protein expression after treatment were investigated.

MATERIALS

All patients underwent 4-monthly intravesical PRP injections with 1-year follow-up. Successful treatment was defined as ≤2 UTI episodes within the preceding 1 year. Bladder biopsies were performed at the first and fourth PRP injection, and specimens were investigated by Western blot for the proteins sonic hedgehog (Shh), CD34, cytokeratin 5 (CK5), CK14, CK20, zonula occludens-1 (ZO-1), E-cadherin, inflammatory proteins tryptase and p38, apoptotic protein BAX (BCL2-associated X protein) and caspase-3, functional proteins M2 (muscarinic receptor 2) and M3, and beta-adrenoceptor-3, with glyceraldehyde phosphate dehydrogenase used as normalizing protein for quantification.

RESULTS

The study enrolled 22 patients with rUTI and 17 controls, with successful outcome in 14 of 22 (63.6%) patients. Compared with controls, Western blot quantification results showed that rUTI patients had lower CD34, CK20, M3, and ZO-1, but higher CK5, BAX, and caspase-3 at baseline. The reduced CD34, CK20, M2, and M3 expressions at baseline were significantly increased after repeat PRP injections. Patients with a successful outcome had significant increase of CD34, Shh, CK20, M2, and M3 expressions after PRP injections.

CONCLUSION

Intravesical PRP repeat injections improve the urothelial cell proliferation and increase the CK 20 expression in umbrella cells. PRP repeat injections have a beneficial effect on bladder urothelium-associated changes in rUTI. Thus, PRP injection may restore urothelial health and prevent UTI recurrence in intractable rUTI.

摘要

目的

本临床研究使用自体膀胱内富含血小板的血浆(PRP)注射治疗复发性尿路感染(rUTI)患者。研究了治疗后尿路上皮增殖、细胞骨架和屏障功能蛋白表达的变化。

材料

所有患者均接受 4 个月的膀胱内 PRP 注射,并进行为期 1 年的随访。成功治疗定义为前 1 年内≤2 次尿路感染发作。在第一次和第四次 PRP 注射时进行膀胱活检,并通过 Western blot 检测 sonic hedgehog(Shh)、CD34、细胞角蛋白 5(CK5)、CK14、CK20、紧密连接蛋白-1(ZO-1)、E-钙粘蛋白、炎性蛋白胰蛋白酶和 p38、凋亡蛋白 BAX(BCL2 相关 X 蛋白)和 caspase-3、功能性蛋白 M2(毒蕈碱受体 2)和 M3 以及β-肾上腺素受体-3,使用甘油醛-3-磷酸脱氢酶作为定量的正常化蛋白。

结果

本研究纳入了 22 例 rUTI 患者和 17 例对照者,22 例患者中有 14 例(63.6%)获得成功。与对照组相比,rUTI 患者的 CD34、CK20、M3 和 ZO-1 表达水平较低,而 CK5、BAX 和 caspase-3 表达水平较高。基线时降低的 CD34、CK20、M2 和 M3 表达在重复 PRP 注射后显著增加。PRP 注射后获得成功的患者的 CD34、Shh、CK20、M2 和 M3 表达显著增加。

结论

膀胱内 PRP 重复注射可改善尿路上皮细胞增殖,并增加伞细胞的 CK20 表达。PRP 重复注射对 rUTI 中膀胱尿路上皮相关变化具有有益作用。因此,PRP 注射可能会恢复尿路上皮健康,预防难治性 rUTI 的尿路感染复发。

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