Therapeutic effect of urine-derived stem cells for protamine/lipopolysaccharide-induced interstitial cystitis in a rat model.
Therapeutic effect of urine-derived stem cells for protamine/lipopolysaccharide-induced interstitial cystitis in a rat model.
复制标题
尿源干细胞对鱼精蛋白/脂多糖诱导的间质性膀胱炎大鼠模型的治疗作用
DOI：
10.1186/s13287-017-0547-9
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发表时间：
2017-05-08
影响因子：
7.5
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Li J;Luo H;Dong X;Liu Q;Wu C;Zhang T;Hu X;Zhang Y;Song B;Li L
背景间质性膀胱炎（IC）是一种慢性炎症疾病，主要发生在膀胱粘膜下和肌肉层。由于IC的病因尚不清楚，目前尚无有效的治疗方法。本研究采用尿源性干细胞（USCs）治疗鱼精蛋白/脂多糖（PS/LPS）诱导的间质性膀胱炎。雌性Sprague-Dawley大鼠60只，随机分为3个实验组（n= 5/组）：假对照组；单独集成电路模型；用USCs （1.2 × 106，悬浮于0.2 ml磷酸盐缓冲盐水（PBS）中）静脉处理的IC动物。结果我们的数据显示，与单独的IC模型组相比，静脉注射USCs对IC动物的膀胱排尿功能有显著改善。Western blot和免疫荧光染色结果显示，静脉注射USCs的IC动物膀胱组织中抗氧化剂和抗凋亡蛋白生物标志物血红素加氧酶(HO)-1、NAD(P)H奎宁氧化还原酶(NQO)-1和Bcl-2的含量明显高于对照组，而假对照组明显低于对照组。此外，IC模型单独组自噬相关蛋白LC3A的表达明显高于静脉注射USCs的IC动物。膀胱组织炎症和凋亡生物标志物(白细胞介素(IL)-6、肿瘤坏死因子（TNF)α、核因子(NF)-κB、caspase 3、Bax）及下游炎症和氧化应激生物标志物（内质网应激和自噬相关蛋白（GRP78、LC3、Beclin1））组间差异有统计学意义。结论suscs通过抑制氧化应激、炎症反应和凋亡过程，恢复了鼠类IC模型的膀胱功能和组织结构，为IC患者的治疗提供了可能。
BackgroundInterstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC.MethodsThis study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague–Dawley rats were randomized into three experimental groups (n= 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1.2 × 106suspended in 0.2 ml phosphate-buffered saline (PBS).ResultsOur data showed that the bladder micturition function was significantly improved in IC animals intravenously treated with USCs compared to those in the IC model alone group. The amount of antioxidants and antiapoptotic protein biomarkers heme oxygenase (HO)-1, NAD(P)H quinine oxidoreductase (NQO)-1, and Bcl-2 within the bladder tissues were significantly higher in IC animals intravenously treated with USCs and lower in the sham controls group as assessed by Western blot and immunofluorescent staining. In addition, the expression of autophagy-related protein LC3A was significantly higher in the IC model alone group than that in IC animals intravenously treated with USCs. Inflammatory biomarkers and apoptotic biomarkers (interleukin (IL)-6, tumor necrosis factor (TNF)α, nuclear factor (NF)-κB, caspase 3, and Bax) and the downstream inflammatory and oxidative stress biomarkers (endoplasmic reticulum stress and autophagy-related protein (GRP78, LC3, Beclin1)) in the bladder tissue revealed statistically different results between groups.ConclusionsUSCs restored the bladder function and histological construction via suppressing oxidative stress, inflammatory reaction, and apoptotic processes in a PS/LPS-induced IC rodent model, which provides potential for treatment of patients with IC.