Sodium tanshinone IIA sulfonate improves inflammation, aortic endothelial cell apoptosis, disseminated intravascular coagulation and multiple organ damage in a rat heat stroke model.
Sodium tanshinone IIA sulfonate improves inflammation, aortic endothelial cell apoptosis, disseminated intravascular coagulation and multiple organ damage in a rat heat stroke model.
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DOI：
10.3892/mmr.2017.6573
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Chen F;Li H;Zhu G;Chen X;Tang Z
本研究旨在探讨丹参酮IIA磺酸钠（STS）对经典中暑（CHS）动物模型炎症反应、主动脉内皮细胞凋亡、弥散性血管内凝血（DIC）和多器官损伤的影响。将中暑（HS）组和经sts处理的中暑（STS-HS）组大鼠置于35℃预热动物温控器（ATC）中。当直肠温度达到43.5℃时为HS发病时间。在HS组中，将大鼠从ATC中取出，在26℃下恢复0、2、6和12小时。在STS-HS组中，大鼠在HS发作后立即接受5-40 mg/kg STS的股静脉注射，随后在26℃下恢复6小时。本研究采用ELISA法检测血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6的水平。采用末端脱氧核苷酸转移酶脱氧尿苷三磷酸镍端标记联合免疫荧光法观察主动脉内皮细胞凋亡数量。HS组大鼠血清TNF-α、IL-1β、IL-6水平及主动脉内皮细胞凋亡数均高于正常对照组。恢复6 h后，HS组血浆凝血酶原时间、活化部分凝血活酶时间及d -二聚体水平均较正常对照组显著升高，血小板计数较正常对照组明显减少。HS组恢复6 h后血清肌酐、血尿素氮、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和乳酸脱氢酶水平升高，多脏器出现组织病理损伤。STS-HS组恢复6 h后细胞因子水平和主动脉内皮细胞凋亡数量均较HS组减少。STS （40 mg/kg）治疗可提高大鼠血清器官损伤指标和凝血功能障碍血浆指标水平，防止多器官组织病理损伤。这些结果表明，STS治疗可能通过减轻炎症反应、主动脉内皮细胞凋亡和DIC来改善多器官损伤。这些结果表明，STS可能有潜力作为治疗HS患者的替代治疗策略。
The aim of the present study was to investigate the effects of sodium tanshinone IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis, disseminated intravascular coagulation (DIC) and multiple organ damage in an animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and STS-treated heat stroke (STS-HS) groups were placed into a pre-warmed animal temperature controller (ATC) at 35°C. The moment at which the rectal temperature reached 43.5°C was considered as the time of onset of HS. In the HS groups, the rats were removed from the ATC and allowed to recover at 26°C for 0, 2, 6 or 12 h. In the STS-HS groups, the rats received femoral vein injections of 5–40 mg/kg STS immediately following the onset of HS and were subsequently placed at a temperature of 26°C to recover for 6 h. In the present study, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were assessed using ELISA, and the numbers of apoptotic aortic endothelial cells were investigated using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling combined with immunofluorescence. In the HS groups, the serum levels of TNF-α, IL-1β and IL-6, as well as the numbers of apoptotic aortic endothelial cells were increased compared with the normothermic control group. Additionally, the plasma prothrombin time, activated partial thromboplastin time and D-dimer level were significantly increased in the HS group compared with the normothermic control group following recovery for 6 h. By contrast, the platelet count was decreased in the HS group compared with the normothermic control group. The serum levels of creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase were increased and histopathological damage to multiple organs was observed in the HS group following recovery for 6 h. In the STS-HS groups, cytokine levels and apoptotic aortic endothelial cell numbers were reduced compared with the HS group after 6 h recovery. STS (40 mg/kg) treatment additionally improved the serum levels of organ injury indicators and plasma indicators of coagulopathy, and prevented histopathological damage to multiple organs. These findings demonstrated that STS treatment may ameliorate multiple organ damage by attenuating inflammatory responses, aortic endothelial cell apoptosis and DIC in CHS. These results suggested that STS may hold potential as an alternative therapeutic strategy for the treatment of patients with HS.