Department of Critical Care Medicine, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
Key Laboratory of Hot Zone Trauma Care and Tissue Repair of PLA, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
Int J Mol Med. 2018 Jan;41(1):137-146. doi: 10.3892/ijmm.2017.3229. Epub 2017 Nov 1.
Intestinal injury-induced bacterial translocation and endotoxemia are important in the pathophysiological process of heatstroke. However, the underlying mechanism remains to be fully elucidated. Previous studies using 2D-gel electrophoresis found that defensin-related cryptdin-2 (Cry-2), an intestinal α-defensin, is upregulated in intestinal tissues during heatstroke in mice, and that treatment with ulinastatin, a multivalent enzyme inhibitor, reduced heat-induced acute lung injury. To investigate the association between Cry-2 and heat stress (HS)-induced intestinal injury and the probable protective role of ulinastatin, the present study examined the intestinal expression of Cry-2 via histopathologic analysis and reverse transcription-quantitative polymerase chain reaction analysis in mice with heatstroke. The heat-stressed mice were exposed to different core temperatures and cooling treatments, and intestinal pathological changes and Chiu scores were determined. Chemical markers of intestinal injury, serum and intestinal concentrations of diamine oxidase (DAO) and D-lactic acid (D-Lac), and serum and intestinal concentrations of Cry-2 were also determined. Correlations were analyzed using Spearman's correlation analysis. It was found that HS upregulated the expression of Cry-2, and the serum and intestinal concentrations of Cry-2 were correlated with the severity of HS-induced intestinal damage, indicated by pathology scores and concentrations of DAO and D-lac. Ulinastatin protected the intestines from HS-induced injury and downregulated the expression of Cry-2, which was also correlated with the extent of intestinal injury. Therefore, ulinastatin administration may be beneficial for patients with heatstroke, and Cry-2 may be a novel predictor of HS-induced intestinal injury.
肠损伤诱导的细菌易位和内毒素血症在中暑的病理生理过程中很重要。然而，其潜在机制仍有待充分阐明。先前使用 2D-凝胶电泳的研究发现，防御素相关的隐穴素-2（Cry-2），一种肠道α-防御素，在中暑小鼠的肠道组织中上调，并且使用多价酶抑制剂乌司他丁治疗可减轻热诱导的急性肺损伤。为了研究 Cry-2 与热应激（HS）诱导的肠道损伤之间的关系，以及乌司他丁可能具有的保护作用，本研究通过组织病理学分析和逆转录定量聚合酶链反应分析，检查了中暑小鼠肠道中 Cry-2 的表达。将热应激小鼠暴露于不同的核心温度和冷却处理，并确定肠道病理变化和邱氏评分。还测定了肠道损伤的化学标志物、血清和肠道中二胺氧化酶（DAO）和 D-乳酸（D-Lac）的浓度以及血清和肠道中 Cry-2 的浓度。使用 Spearman 相关分析进行相关性分析。结果发现，HS 上调了 Cry-2 的表达，血清和肠道中 Cry-2 的浓度与 HS 诱导的肠道损伤的严重程度相关，由病理评分和 DAO 和 D-Lac 的浓度来表示。乌司他丁保护肠道免受 HS 诱导的损伤，并下调 Cry-2 的表达，这也与肠道损伤的程度相关。因此，乌司他丁的给药可能对中暑患者有益，而 Cry-2 可能是 HS 诱导的肠道损伤的一个新的预测指标。
