a Department of Hemopurification Center , The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology , Luoyang , China.
Immunopharmacol Immunotoxicol. 2018 Apr;40(2):168-172. doi: 10.1080/08923973.2018.1424898. Epub 2018 Jan 22.
The objective of this study is to investigate the effect of combination of umbilical cord-derived mesenchymal stem cell (UC-MSC) and vitamin E (VitE) on inflammation in mice with acute kidney injury (AKI).
UC-MSCs were isolated from pregnant wistar mice and cultured. A total of 90 female wistar mice were randomly divided into control group, AKI group, AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC group (18 mice in each group) which were given no treatment, normal saline, VitE, UC-MSC, and VitE + UC-MSC, respectively. The renal pedicles on both sides were clipped for 50 min with micro-artery clips to induce AKI. Six mice were sacrificed at days 1, 3, and 7, while blood and kidney tissues were collected to detect levels of blood urea nitrogen (BUN) and creatinine (Scr). Kidney tissues were stained by HE staining to observe pathological changes; levels of interleukin-lβ, TNF-α, interleukin-10, and β-FGF were measured by ELISA.
Compared with the control group, AKI mice showed higher levels of serum BUN and Scr, tubular swelling and necrosis suggesting that AKI model was successfully established. Mice in AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC presented better renal function than mice of AKI group. Mice from AKI + VitE + UC-MSC group showed the best renal function with the least renal tubular injury (p < .05). ELISA detection revealed that pro-inflammatory cytokines were significantly increased and anti-inflammatory cytokine levels were significantly decreased in all time points (p < .05). VitE, UC-MSC, and VitE + UC-MSC resulted in the increase of anti-inflammatory cytokine levels and reduction of pro-inflammatory cytokine levels and the combination of VitE and UC-MSC performed favorable effect in the suppression of inflammation in AKI mice (p < .05).
Combination of UC-MSC and VitE significantly inhibited inflammatory reaction in kidney through the regulation of inflammatory cytokines in the microenvironment of kidney with AKI. Combination of UC-MSC and VitE presented therapeutic effect on AKI than the single use of UC-MSC or VitE.
本研究旨在探讨脐带间充质干细胞（UC-MSC）与维生素 E（VitE）联合应用对急性肾损伤（AKI）小鼠炎症的影响。
从妊娠 Wistar 小鼠中分离 UC-MSCs 并进行培养。将 90 只雌性 Wistar 小鼠随机分为对照组、AKI 组、AKI+VitE 组、AKI+UC-MSC 组和 AKI+VitE+UC-MSC 组（每组 18 只），分别给予无处理、生理盐水、VitE、UC-MSC 和 VitE+UC-MSC。用微动脉夹夹闭双侧肾蒂 50min 诱导 AKI。处死 6 只小鼠，分别于第 1、3、7 天采集血和肾组织，检测血尿素氮（BUN）和肌酐（Scr）水平。HE 染色观察肾组织病理变化；ELISA 法检测白细胞介素-1β、TNF-α、白细胞介素-10 和 β-FGF 水平。
与对照组相比，AKI 组小鼠血清 BUN 和 Scr 水平升高，肾小管肿胀坏死，表明 AKI 模型建立成功。AKI+VitE 组、AKI+UC-MSC 组和 AKI+VitE+UC-MSC 组小鼠肾功能优于 AKI 组。AKI+VitE+UC-MSC 组小鼠肾功能最佳，肾小管损伤最小（p<.05）。ELISA 检测发现，各时间点促炎细胞因子水平均显著升高，抗炎细胞因子水平均显著降低（p<.05）。VitE、UC-MSC 和 VitE+UC-MSC 均能增加抗炎细胞因子水平，降低促炎细胞因子水平，且 VitE 和 UC-MSC 联合应用在抑制 AKI 小鼠炎症反应方面效果较好（p<.05）。
UC-MSC 与 VitE 联合应用通过调节 AKI 肾组织微环境中的炎症细胞因子，显著抑制肾脏炎症反应。UC-MSC 与 VitE 联合应用对 AKI 的治疗效果优于 UC-MSC 或 VitE 单一应用。
