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地塞米松对创伤休克大鼠肝脏热休克蛋白70表达的影响

Effects of dexamethasone on heat shock protein 70 expression in liver in a rodent model of hemorrhagic shock
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摘要 目的探讨地塞米松对创伤休克肝组织中热休克蛋白70(HSP70)的表达变化以及对肝脏结构和功能的影响。方法雄性健康Wistar大鼠72只,采用双侧股骨骨折伴失血性休克创伤模型,随机分成正常对照组12只,创伤休克组30只,创伤休克地塞米松组30只,地塞米松采用腹腔注射给药。动态观察伤后0.5、2、4、6、8h大鼠肝组织HSP70、肝脏病理、肝功能、TNF—α、IL-6等变化。HSP70采用免疫印迹法测定其蛋白含量,并进行计算机图像分析。结果HSP70伤后2h较正常对照相比差异有统计学意义,伤后6h达到高峰,伤后8h仍持续在较高水平。TNF-α、IL-6伤后逐渐升高,并于伤后6h达到高峰,和正常组相比,差异有统计学意义。光镜下伤后4h肝窦内淤血明显,有大量炎性细胞浸润;血清ALT、TB伤后4h开始增高,8h达到峰值。腹腔注射地塞米松后,HSP70在伤后各个时相点的表达均较创伤休克组明显增强,峰值仍然在伤后6h。TNF—α、IL-6伤后各个时相点均迅速回落。肝脏大体淤血、肿胀明显减轻;光镜下伤后4h肝细胞变性明显好转,肝窦内见淤血减轻,仅见少许淋巴细胞及中性粒细胞浸润;血清ALT、TB明显下降。结论地塞米松可增强HSP70在创伤失血性休克后肝组织中的表达,可减轻创伤失血性休克后肝脏的继发性损害,表明地塞米松对创伤休克后肝脏的保护作用与HSP70密切相关。 Objective To study effects of dexamethasone on heat shock protein 70 (HSP70) expression in liver as well as on the changes of hepatic function and ultrastructure in a rodent model of hemorrhagic shock after trauma. Methods Hemorrhagic shock was produced by inducing bilateral femoral fractures in male Wistar rats. Dexamethasone Was used by intraperitoneal injection. A total of 72 adult male Wistar rats were randomly divided into 3 groups : control group ( n = 12 ) , trauma group ( n = 30) , and dexamethasone followed by trauma shock group ( n = 30 ). Measurements of hepatic HSP70, hepatic function markers, TNF - α and IL - 6 were dynamically obtained at 0.5, 2, 4, 6, 8 h 'after trauma. Histopathologieal changes in liver tissues were also noted. The expression of HSP70 in hepatic tissue was assayed by western blot and then analyzed with computer imaging system. Results In rats with trauma shock, HSP70 expression increased significantly compared to the control group, peaking at 6 hour post trauma. Hepatic tissue TNF-α and IL-6, as well as serum alanine transferase (ALT) and total bilirubin (TB) also rise significantly, peaking at 8 hour post trauma. Light microscopy revealed hepatic congestion with infiltration of inflammatory cells into hapatic sinusoid at 8 hour in the trauma shock group. After using dexamethasone, expression of HSP70 increased significantly compared to the trauma shock group. Levels TNF-α and IL-6, as well as ALT and TB also lowered post trauma, and hepatic congestion as well as hepatic degeneration were ameliorated, with minimal inflammatory infiltrates noted in the sinusoids. Conclusions Dexamethasone may enhance expression of HSP70 in liver in a rodent model of hemorrhagic shock after trauma, and ameliorate hapatic secondary lesion. It is indicated that dexamethasone is correlated to HSP70 in the course of protecting liver after trauma with hemorrhagic shock.
出处 《中国急救医学》 CAS CSCD 北大核心 2009年第3期238-241,共4页 Chinese Journal of Critical Care Medicine
基金 重庆市自然科学基金项目(No.2004BB5068,No.2008BB5138)
关键词 创伤 失血性休克 肝脏 热休克蛋白 地塞米松 Trauma Hemorrhagic shock Liver Heat shock protein Dexamethasone
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