CD11c＋F4／80叫肾脏固有树突状细胞在肾脏缺血再灌注损伤中的作用

CD11c＋ F4/80 renal resident DCs in kidney ischemia reperfusion injury

目的研究CD11c＋F4／80肾脏固有树突状细胞（rDC）在肾脏缺血再灌注（IR）损伤中的作用及机制。方法采用C．FVB-Tg（Itgax-DTR／GFP）57Lan／J小鼠（以下简称DTR／GFP小鼠）经不同剂量白喉毒素处理18h后，检测小鼠肾脏rDC的清除效果及小鼠体质量的变化，筛选最佳注射剂量进行后续实验。取DTR／GFP小鼠，注射白喉毒素（16ng／g体质量）18h后，建立IR模型，于再灌注24h后，检测肾功能变化、肾组织病理改变、rIX2比例及血清中的白细胞介素10（IL-10）、肿瘤坏死因子-α（TNF-α）、MCP-1等细胞因子变化。结果小鼠注射16ng／g体质量白喉毒素后可有效清除rDC并维持小鼠最小损伤。清除rDC后小鼠肾功能损害明显加重，血肌酐和尿素氮明显升高（P〈0．05），病理可见肾小管组织的损伤程度与炎症细胞浸润明显增加，小鼠血清中TNF-α、IL-6、MCP-1等表达均显著升高（P〈0．05），IL-10的表达则呈显著下调（P〈0．05）。结论CD11c＋F4／80-rDC在肾脏IR损伤中发挥抗炎和组织保护作用。

Objective To study the role of CD11 c＋ F4/80- renal resident DCs in kidney ischemia reperfusion injury, and investigate the underlining mechanism. Method The optimal diphtherotoxin （DT） dose was screened. C. FVB-Tg （Itgax-DTR/GFP） 57Lan/J （DTR/GFP） mice were intraperitoneally injected with 0, 8, 16, and 24 ng/g weight of DT, and the clearance of rDC and mice weight loss were detected 18 h later. DTR/GFP mice were injected with DT and PBS 18 h before the bilateral kidney ischemia reperfusion models were established. 24 h after reperfusion, kidney samples were harvested to perform histological analysis and FACS analysis. Blood samples were also harvested to determine serum creatinine and urea nitrogen, and the expression of serum TNF-α, IL-I0, IL-6 and MCP-1 was measured with ELISA kit. Result The intraperitoneal injection of 16 ng/g weight DT displayed highest clearance of renal resident DCs and minimal weight loss in DTR/GFP mice. In the absence of CD11 c＋ F4/80- renal resident DCs, bilateral kidney ischemia resulted significantly increased kidney damage as shown by serum creatinine （206. 7 ± 31.26 vs. 153.1 ± 22. 65, P〈0. 05）, urea nitrogen （97. 17 ± 13.72 vs. 73.14 ±12. 94, P 〈 0.05）, and kidney histological analysis. Furthermore, serum expression levels of TNF-α （97.25 ± 7. 5 vs. 31.25 ± 4. 57, P〈0. 01）, IL-6 （287.3±45.61 vs. 172.5±11.9, P〈0.05）, andMCP-1 （802.8＋87.8i vs. 330.3＋50.26, P〈 0. 05） were also significantly increased, and those of IL-10 （26. 75± 5.32 vs. 52. 5 ± 6. 46, P〈0. 05） decreased after the CD11c ＋ F4/80- renal resident DCs being eliminated. Conclusion CD11c＋ F4/80- renal resident DCs play an anti-inflammatory role in kidney ischemia reperfusion injury.