Division of Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Inflamm Res. 2011 Mar;60(3):299-307. doi: 10.1007/s00011-010-0268-3. Epub 2010 Dec 12.
This study investigates the effect of a superoxide dismutase mimetic, MnTMPyP, on pro- and anti-inflammatory cytokines in acute renal ischemia-reperfusion (IR).
Male Sprague-Dawley rats underwent bilateral clamping of the renal arteries for 45 min followed by 1, 4, or 24 h of reperfusion. A subset of animals was treated with MnTMPyP (5 mg/kg, i.p.) or saline. Porcine proximal tubular epithelial cells were ATP-depleted for 4 h followed by recovery for 2 h.
Cytokines were analyzed by ELISA, and ED1(+) macrophages and CD8(+) T lymphocytes by immunohistochemistry. Statistical analysis was performed using ANOVA.
MnTMPyP attenuated the IR-mediated increase in serum creatinine and circulating levels of interleukin (IL)-2 following 24 h of reperfusion. Furthermore, treatment attenuated increases in tissue levels of tumor necrosis factor (TNF)-α, IL-2, IL-4, and IL-13. MnTMPyP partially prevented the IR-induced infiltration of ED1(+) macrophages and CD8(+) T lymphocytes in the kidney. ATP depletion-recovery of porcine proximal tubular epithelial cells resulted in decreased IL-6 and IL-10 levels, and MnTMPyP partially restored these cytokines.
These results show that MnTMPyP is partially effective in reducing inflammation associated with renal IR and that reactive oxygen species play a role in modulating both pro- and anti-inflammatory pathways in acute kidney injury.
本研究旨在探讨超氧化物歧化酶模拟物 MnTMPyP 对急性肾缺血再灌注（IR）中促炎和抗炎细胞因子的影响。
雄性 Sprague-Dawley 大鼠行双侧肾动脉夹闭 45 分钟，随后再灌注 1、4 或 24 小时。部分动物接受 MnTMPyP（5mg/kg，腹腔注射）或生理盐水治疗。猪近端肾小管上皮细胞在 ATP 耗竭 4 小时后进行 2 小时恢复。
通过 ELISA 分析细胞因子，通过免疫组织化学分析 ED1(+)巨噬细胞和 CD8(+)T 淋巴细胞。采用方差分析进行统计学分析。
MnTMPyP 减轻了 24 小时再灌注后血清肌酐和循环白细胞介素（IL）-2 升高，减轻了组织肿瘤坏死因子（TNF）-α、IL-2、IL-4 和 IL-13 水平的升高。MnTMPyP 部分预防了 IR 诱导的肾脏中 ED1(+)巨噬细胞和 CD8(+)T 淋巴细胞浸润。猪近端肾小管上皮细胞的 ATP 耗竭-恢复导致 IL-6 和 IL-10 水平降低，而 MnTMPyP 部分恢复了这些细胞因子。
这些结果表明，MnTMPyP 在减轻与肾 IR 相关的炎症方面具有一定的效果，活性氧在调节急性肾损伤中的促炎和抗炎途径中起作用。
