共 31 条
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.
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页码:248 / 261
页数:14
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