Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat

被引:68
作者
Chen, Yen-Ta [1 ,2 ]
Chiang, Hsin-Ju [2 ,3 ]
Chen, Chih-Hung [2 ,4 ]
Sung, Pei-Hsun [2 ,5 ]
Lee, Fan-Yen [2 ,6 ]
Tsai, Tzu-Hsien [2 ,5 ]
Chang, Chia-Lo [2 ,7 ]
Chen, Hong-Hwa [2 ,7 ]
Sun, Cheuk-Kwan [8 ]
Leu, Steve [9 ]
Chang, Hsueh-Wen [2 ,10 ]
Yang, Chih-Chao [2 ,11 ]
Yip, Hon-Kan [2 ,5 ,9 ,12 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Urol, Kaohsiung 83301, Taiwan
[2] Chang Gung Univ Coll Med, Kaohsiung, Taiwan
[3] Kaohsiung Chang Gung Mem Hosp, Dept Obstet & Gynecol, Kaohsiung 83301, Taiwan
[4] Kaohsiung Chang Gung Mem Hosp, Div Gen Med, Dept Internal Med, Kaohsiung 83301, Taiwan
[5] Kaohsiung Chang Gung Mem Hosp, Div Cardiol, Dept Internal Med, Kaohsiung 83301, Taiwan
[6] Kaohsiung Chang Gung Mem Hosp, Div Thorac & Cardiovasc Surg, Dept Surg, Kaohsiung 83301, Taiwan
[7] Kaohsiung Chang Gung Mem Hosp, Div Colorectal Surg, Dept Surg, Kaohsiung 83301, Taiwan
[8] I Shou Univ, E DA Hosp, Dept Emergency Med, Kaohsiung, Taiwan
[9] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 80424, Taiwan
[10] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung 83301, Taiwan
[11] Kaohsiung Chang Gung Mem Hosp, Div Nephrol, Dept Internal Med, Kaohsiung 83301, Taiwan
[12] Kaohsiung Chang Gung Mem Hosp, Inst Shock Wave Med & Tissue Engn, Kaohsiung 83301, Taiwan
关键词
acute interstitial cystitis; adipose-derived mesenchymal stem cells; cyclophosphamide; inflammation; oxidative stress; melatonin; ISCHEMIA-REPERFUSION INJURY; OXIDATIVE STRESS; KIDNEY INJURY; TRANSPLANTATION; EPIDEMIOLOGY;
D O I
10.1111/jpi.12164
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:248 / 261
页数:14
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