Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat
Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat
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DOI：
10.1111/jpi.12164
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发表时间：
2014-10-01
影响因子：
10.3
通讯作者：
Yip, Hon-Kan
中科院分区：
文献类型：
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作者：
Chen, Yen-Ta;Chiang, Hsin-Ju;Yip, Hon-Kan
这项研究测试了这样的假设：褪黑激素和脂肪源性间充质干细胞（ADMSC，静脉注射 1.2 x 10(6)）联合治疗对环磷酰胺 (CYP 150 mg/kg) 诱导的大鼠急性间质性膀胱炎 (AIC) 具有卓越的保护作用。雄性成年Sprague-Dawley大鼠的治疗如下：假手术对照、单独AIC、AIC+褪黑激素、AIC+ADMSC和AIC+褪黑激素+ADMSC。当使用褪黑激素时，给药剂量如下：CYP后30分钟20mg/kg，CYP后6小时和18小时50mg/kg。 AIC 大鼠的 24 小时尿量、尿白蛋白水平和血尿严重程度最高，对照组最低；同样，AIC + 褪黑激素治疗的大鼠的尿量高于 AIC + ADMSC 和 AIC + 褪黑激素 + ADMSC 治疗的大鼠；在所有情况下，P < 0.001。 CD14+、CD74+、CD68+、MIP+、Cox-2+、P+物质的数量，IL-6、IL-12、RANTES、TNF-α、NF-kappa B、MMP-9、iNOS（即炎症生物标志物）的细胞和蛋白表达量、糖胺聚糖水平、氧化蛋白表达量、活性氧蛋白表达量（NOX-1、NOX-2、与五组中的血尿相比，膀胱组织中的NOX-4）表现出相同的模式（均P < 0.0001）。各组上皮层完整性和胶原沉积面积与血尿表现出相反的模式（P < 0.0001）。抗氧化剂（GR、GPx、HO-1、NQO 1）的细胞表达较 AIC + 褪黑素 + ADMSC 对照组显着逐渐增加（所有 P < 0.0001）。褪黑激素和 ADMSC 的联合治疗方案在预防 CYP 诱导的 AIC 方面优于单独使用任何一种治疗方案。
This study tests the hypothesis that combined melatonin and adipose-derived mesenchymal stem cell (ADMSC, 1.2 x 10(6) given intravenously) treatment offer superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC + melatonin + ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at 30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine volume, urine albumin level, and severity of hematuria were highest in AIC rats and lowest in the controls; likewise urine volume was higher in AIC + melatonin rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases, P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells and protein expression of IL-6, IL-12, RANTES, TNF-alpha, NF-kappa B, MMP-9, iNOS (i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4) in the bladder tissue exhibited an identical pattern compared with that of hematuria among the five groups (all P < 0.0001). The integrity of epithelial layer and area of collagen deposition displayed an opposite pattern compared to that of hematuria among all groups (P < 0.0001). The cellular expressions of antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of melatonin and ADMSC was superior to either alone in protecting against CYP-induced AIC.