Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.
Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.
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DOI：
10.1186/scrt212
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发表时间：
2013-05-31
影响因子：
7.5
通讯作者：
Yip HK
中科院分区：
文献类型：
--
作者：
Chen YT;Yang CC;Zhen YY;Wallace CG;Yang JL;Sun CK;Tsai TH;Sheu JJ;Chua S;Chang CL;Cho CL;Leu S;Yip HK
本研究验证了环孢素(CsA)支持的同基因脂肪间充质干细胞(ADMSC)治疗对急性缺血再灌注(IR)肾损伤的缓解作用优于单独使用任何一种治疗的假说。成年SD大鼠40只，随机分为假手术对照组(Sham)、缺血再灌注损伤(IR)组、缺血再灌注+环孢素A(CsA)组、同基因ADMSC(1.2×106)组和IR+CsA-ADMSC组。IR后72小时，2组血肌酐水平最高，1组最低，3、4组显著高于5组(组间比较均P<0.05)，3、4组间差异无统计学意义(P>0.05)。IR组肾组织炎症标志物(基质金属蛋白酶-9、RANTES、肿瘤坏死因子-α)、蛋白(肿瘤坏死因子-α、核因子-κB、细胞间黏附分子-1、血小板衍生生长因子)和细胞(CD68+)水平与肌酐水平的变化规律相似(组间比较均P<0.05)。氧化应激(氧化蛋白)、活性氧(NADPH氧化酶NOX-1、NOX-2)、细胞凋亡(Bc l-2相关X蛋白、caspase-3和聚ADP核糖聚合酶)和DNA损伤(磷酸化H_2A组蛋白家族成员X阳性、增殖细胞核抗原阳性细胞)的蛋白表达与炎症介质相似(组间比较均P<；0.05)。抗氧化生物标志物在细胞水平(谷胱甘肽过氧化物酶、谷胱甘肽还原酶、血红素氧合酶-1)和蛋白水平(NADPH脱氢酶(苯醌)-1、HO-1、内皮一氧化氮合酶)和内皮祖细胞标志物(C-X-C趋化因子受体4阳性，基质细胞衍生因子-1α阳性)的表达在第1和第2组最低，第3和第4组较高，第5组最高(组间比较均P<；0.05)。CsA+ADMSCs联合治疗可改善对急性IR肾损伤的保护作用。
This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia–reperfusion (IR) kidney injury to either therapy alone. Adult Sprague–Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2–associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P <0.05 for inter-group comparisons). Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury.
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影响因子：
13.6
作者：
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通讯作者：
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