Bone marrow-derived mononuclear cell therapy can attenuate systemic inflammation in rat heatstroke.
Bone marrow-derived mononuclear cell therapy can attenuate systemic inflammation in rat heatstroke.
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DOI：
10.1186/s13049-018-0566-2
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发表时间：
2018-11-16
期刊：
影响因子：
--
通讯作者：
Shimazu T
中科院分区：
文献类型：
--
作者：
Umemura Y;Ogura H;Matsuura H;Ebihara T;Shimizu K;Shimazu T
这项研究是为了深入了解中暑急性全身性炎症的新治疗方法。骨髓源性单核细胞（bmmmnc）分泌抗炎蛋白，对急性炎症具有保护作用。最近有证据表明，bmmnc移植可减轻局部心肌再灌注引起的急性组织损伤和脂多糖引起的肺功能障碍。我们评估了bmmnc是否能减轻严重中暑引起的全身炎症反应。将麻醉的12周龄雄性Wistar大鼠进行热应激（41.8°C， 30分钟），同时或不移植bmmnc。骨髓细胞取自其他Wistar大鼠的股骨和胫骨。采用密度离心分离bmmnc，溶解于磷酸盐缓冲盐水（PBS）中，热应激后立即静脉注射（hs - bmmnc组）。对照组给予等量PBS，假手术组在没有热应激的情况下进行相同的治疗。hs - bmmnc组的7天生存率较对照组显著提高（83.3%比41.7%）。bmmnc移植在热应激后3、6和12小时显著抑制血清促炎介质水平，如肿瘤坏死因子- α、白细胞介素-6和组蛋白H3。此外，与对照组相比，bmmnc组在热应激后6和12 h血清中血管内皮糖萼层主要成分syndecan-1的升高明显受到抑制。组织学分析显示，热应激后6 h，对照组肺泡隔水肿明显，肺血管内皮损伤明显，hs - bmmnc组形态学改变有所改善。此外，对绿色荧光蛋白转基因大鼠的bmmnc进行组织学分析显示，移植的bmmnc在热应激后24小时迁移到肺、肾和脾脏，但没有移植到宿主组织。在大鼠中暑模型中，bmmnc移植减轻了急性全身炎症和血管内皮损伤，减轻了器官功能障碍，提高了生存率。这些发现提供了一种可能的治疗中暑的策略。
This study was performed to gain insights into novel therapeutic approaches for acute systemic inflammation in heatstroke. Bone marrow-derived mononuclear cells (BMMNCs) secrete anti-inflammatory proteins and have protective effects against acute inflammation. Recent evidence suggested that transplantation of BMMNCs can reduce the acute tissue injury caused by regional myocardial reperfusion and the lung dysfunction induced by lipopolysaccharides. We evaluated whether BMMNCs attenuate systemic inflammatory response induced by severe heatstroke. Anesthetized 12-week-old male Wistar rats were subjected to heat stress (41.8 °C for 30 min) with/without transplantation of BMMNCs. Bone marrow cells were harvested from the femur and tibia of other Wistar rats. BMMNCs were separated by density centrifugation, dissolved in phosphate-buffered saline (PBS), and injected intravenously immediately after heat stress (HS-BMMNCs group). The control group was administered an equal volume of PBS, and the sham group underwent the same procedure without heat stress. Seven-day survival improved significantly in the HS-BMMNCs group versus control group (83.3% vs 41.7%). Transplantation of BMMNCs significantly suppressed serum levels of pro-inflammatory mediators, such as tumor necrosis factor-alpha, interleukin-6 and histone H3 at 3, 6, and 12 h after heat stress. Besides, the elevation of serum syndecan-1, a main component of the vascular endothelial glycocalyx layer, in the BMMNCs group was significantly suppressed compared to that in the control group at 6 and 12 h after heat stress. Histological analysis revealed that edema of the alveolar septum and vascular endothelial injury in the lung were evident in the control group 6 h after heat stress, whereas the morphological alteration was ameliorated in the HS-BMMNCs group. Also, histological analysis using BMMNCs derived from green fluorescent protein transgenic rats showed that the transplanted BMMNCs migrated into lung, kidney, and spleen at 24 h after heat stress but did not engraft to host tissues. Transplantation of BMMNCs attenuated acute systemic inflammation and vascular endothelial injury, reduced organ dysfunction, and improved survival in a rat heatstroke model. These findings provide a possible therapeutic strategy against critical heatstroke.
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影响因子：
38.9
作者：
Hausfater, Pierre;Megarbane, Bruno;Riou, Bruno
通讯作者：
Riou, Bruno
影响因子：
3.7
作者：
Hirose T;Hamaguchi S;Matsumoto N;Irisawa T;Seki M;Tasaki O;Hosotsubo H;Yamamoto N;Yamamoto K;Akeda Y;Oishi K;Tomono K;Shimazu T
通讯作者：
Shimazu T
影响因子：
7.1
作者：
Hifumi T;Kondo Y;Shimizu K;Miyake Y
通讯作者：
Miyake Y
DOI：
10.1161/atvbaha.107.158709
发表时间：
2008-06-01
影响因子：
8.7
作者：
Roberts, George T.;Ghebeh, Hazem;Bouchama, Abderrezak
通讯作者：
Bouchama, Abderrezak
影响因子：
--
作者：
Argaud, Laurent;Ferry, Tristan;Robert, Dominique
通讯作者：
Robert, Dominique