Zhang Jian-Bo, Wang Xiao-Qiao, Lu Guo-Lin, Huang Huan-Sen, Xu Shi-Yuan
Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Clin Exp Pharmacol Physiol. 2017 Dec;44(12):1232-1240. doi: 10.1111/1440-1681.12811. Epub 2017 Oct 12.
Acute kidney injury (AKI) represents a group of complicated syndromes with a high mortality rate. The administration of adipose-derived mesenchymal stem cells (ADMSCs) has been tested as a possible treatment method for AKI. The long-term evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal protection of ADMSCs are limited. In this study we have established a rat AKI model induced by IR and investigated the possible protective effects of ADMSCs. Adult Sprague-Dawley (SD) rats were divided into three groups (n = 6/each group). The MOCK group was as the normal control. Rats in the IR-AKI and IR-AKI+ADMSCs groups were subjected to IR injury by clamping both renal pedicles for 40 minutes. Rats in the MOCK and IR-AKI groups were injected with PBS via the tail vein as negative treatment controls. Rats in the IR-AKI+ADMSCs group received ADMSCs therapy (2 × 10 cells were injected into the rats via the tail vein). We found that ADMSC transplantation restored the pathologic morphology induced by IR-AKI to normal compared with the MOCK group, suggesting the reparative function of ADMSCs in kidney tissues. Compared with IR-induced AKI alone, ADMSC treatment significantly decreased the number of apoptotic cells, the level of total urinary protein and serum creatinine, the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ, TNF-α, IFN-γ, and TGF-β), and the inflammation-associated proteins (HGF and SDF1), but increased the expression of the anti-inflammatory cytokine, IL-10, and the anti-apoptotic regulator, Bcl-2. Our data have indicated that ADMSC transplantation may protect against IR-induced AKI by anti-apoptotic and anti-inflammatory effects.
急性肾损伤(AKI)是一组复杂的综合征,死亡率很高。脂肪来源的间充质干细胞(ADMSCs)的应用已被作为AKI的一种可能治疗方法进行了测试。对缺血/再灌注(IR)诱导的AKI的长期评估以及ADMSCs可能的肾脏保护作用有限。在本研究中,我们建立了IR诱导的大鼠AKI模型,并研究了ADMSCs可能的保护作用。成年Sprague-Dawley(SD)大鼠分为三组(每组n = 6)。假手术组作为正常对照组。IR-AKI组和IR-AKI+ADMSCs组的大鼠通过夹闭双侧肾蒂40分钟进行IR损伤。假手术组和IR-AKI组的大鼠通过尾静脉注射PBS作为阴性治疗对照。IR-AKI+ADMSCs组的大鼠接受ADMSCs治疗(通过尾静脉向大鼠注射2×10个细胞)。我们发现,与假手术组相比,ADMSC移植使IR-AKI诱导的病理形态恢复正常,表明ADMSCs在肾组织中的修复功能。与单独的IR诱导的AKI相比,ADMSC治疗显著减少了凋亡细胞数量、总尿蛋白和血清肌酐水平、促炎细胞因子(IL-6、TNF-α、IL-1β、IFN-γ、TNF-α、IFN-γ和TGF-β)以及炎症相关蛋白(HGF和SDF1)的表达,但增加了抗炎细胞因子IL-10和抗凋亡调节因子Bcl-2的表达。我们的数据表明,ADMSC移植可能通过抗凋亡和抗炎作用预防IR诱导的AKI。