Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury

被引：159

作者：

Chen, Hong-Hwa ^{[1
,2
]}

Lin, Kun-Chen ^{[2
,3
]}

Wallace, Christopher G. ^{[4
]}

Chen, Yen-Ta ^{[2
,5
]}

Yang, Chih-Chao ^{[2
,6
]}

Leu, Steve ^{[2
,7
]}

Chen, Yi-Ching ^{[2
,8
]}

Sun, Cheuk-Kwan ^{[9
]}

Tsai, Tzu-Hsien ^{[2
,8
]}

Chen, Yung-Lung ^{[2
,8
]}

Chung, Sheng-Ying ^{[2
,8
]}

Chang, Chia-Lo ^{[1
,2
]}

Yip, Hon-Kan ^{[2
,8
,10
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Div Colorectal Surg, Dept Surg, Kaohsiung 83301, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Dept Anesthesiol, Kaohsiung 83301, Taiwan

[4] Univ S Manchester Hosp, Dept Plast Surg, Manchester M20 8LR, Lancs, England

[5] Kaohsiung Chang Gung Mem Hosp, Div Urol, Dept Surg, Kaohsiung 83301, Taiwan

[6] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Nephrol, Kaohsiung 83301, Taiwan

[7] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung 83301, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, Kaohsiung 83301, Taiwan

[9] I Shou Univ, E DA Hosp, Dept Emergency Med, Kaohsiung, Taiwan

[10] Kaohsiung Chang Gung Mem Hosp, Inst Shock Wave Med & Tissue Engn, Kaohsiung 83301, Taiwan

来源：

JOURNAL OF PINEAL RESEARCH | 2014年 / 57卷 / 01期

关键词：

acute kidney injury; adipose-derived mesenchymal stem cells; inflammation; melatonin; oxidative stress; sepsis syndrome; ISCHEMIA-REPERFUSION INJURY; INTENSIVE-CARE UNITS; SEPTIC SHOCK; OXIDATIVE STRESS; INFLAMMATORY RESPONSE; ORGAN DYSFUNCTION; T-CELLS; REPAIR; MODEL; RAT;

D O I：

10.1111/jpi.12140

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-alpha level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper-, cytoxic-, and regulatory-T cells at post-CLP 72 hr exhibited the same pattern as that of circulating TNF-alpha among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, and higher in CLP-A-ADMSC than in CLP-melatonin-A-ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF-1 alpha, NF-kappa B, MMP-9, MIP-1, IL-1 beta), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-beta) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin-than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.

引用

页码：16 / 32

页数：17

共 41 条

[41]

Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells [J].

Zhu, Weiquan ;

Chen, Jinghai ;

Cong, Xiangfeng ;

Hu, Shengshou ;

Chen, Xi .

STEM CELLS, 2006, 24 (02) :416-425

← 1 2 3 4 5 →