p38丝裂原活化蛋白激酶抑制剂对脓毒症大鼠多器官损伤的保护作用研究
马中富 乐胜 梁艳冰 詹红 唐皓 荆小莉【摘要】 目的: 探讨脓毒症致多器官损伤的原因，以及p38丝裂原活化蛋白激酶(MAPK)抑制剂的保护作用和机制。方法:采用盲肠结扎穿刺术(CLP)制备脓毒症大鼠模型，治疗组采用术前给予p38MAPK抑制剂SB203580灌胃。在不同时间点观察大鼠血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)以及生化指标如丙氨酸转氨酶(ALT)、尿素氮(BUN)、肌酐(Cr)、肌酸磷酸激酶-同工酶(CPK-MB)浓度的变化。结果: CLP术后大鼠血清TNF-α、IL-1β显著升高，ALT、BUN、Cr、CPK-MB也进行性升高；血清ALT、BUN、Cr、CPK-MB变化与TNF-α、IL-1β呈显著正相关。应用SB203580后，血清TNF-α、IL-1浓度显著降低，同时ALT、BUN、Cr、CPK-MB也降低。结论: TNF-α、IL-1β的大量释放是脓毒症致多器官损伤的原因之一，通过调控p38MAPK信号转导通路可对脓毒症所致多器官损伤起保护作用。
【关键词】 脓毒症；p38丝裂原活化蛋白激酶； 肿瘤坏死因子-α；白细胞介素-1β
Protective effect of p38 mitogen activated protein kinase inhibitor on organs in sepsis in rats
MA Zhong-fu, LE Sheng, LIANG Yan-bing, ZHAN Hong, TANG Hao, JING Xiao- li.
Emergency Department, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
【Abstract】 OBJECTIVE:：To investigate the pathogenesis of multiorgan injury and the protective of p38 mitogen activated protein kinase(p38MAPK) inhibitor on organs in sepsis. METHODS:：Cecal ligation and puncture was adopted to reproduce sepsis model. The levels of serum biochemical parameters 〔including alanine aminotransferase (ALT), blood urea nitrogen(BUN), creatinine(Cr), MB isoenzyme of creatine phosphokinase (CPK-MB), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) were determined at different time points. RESULTS：The levels of ALT, BUN, Cr, CPK-MB, TNF-α and IL-β rose progressively after the cecal ligation operation. The levels of TNF-α and IL-1β showed a significant correlation with levels of ALT, BUN, Cr, CPK-MB. After the administration of p38MAPK inhibitor, SB203580, the level of TNF-α and IL-1β were found to decrease evidently, and the injury to multiple organs was alleviated. CONCLUSION:：Excessive secretion of TNF-α and IL-β may be the main cause of multiorgan injury in sepsis. Modulation of the p38MAPK pathway may protect multiorgan injury in sepsis. ......
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