Jian Bixi, Hsieh Chi-Hsun, Chen Jianguo, Choudhry Mashkoor, Bland Kirby, Chaudry Irshad, Raju Raghavan
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biochim Biophys Acta. 2008 Nov;1782(11):621-6. doi: 10.1016/j.bbadis.2008.08.007. Epub 2008 Aug 28.
Hemorrhagic trauma leads to organ dysfunction, sepsis and death. There is abnormal production of proinflammatory cytokines by Kupffer cells, tissue hypoxia and liver injury following trauma-hemorrhage. The physiological conditions consequent to trauma-hemorrhage are consistent with factors necessary to initiate endoplasmic reticulum (ER) stress and unfolded protein response. However, the contribution of ER stress to apoptosis and liver injury after trauma-hemorrhage is not known. In the present study ER stress was investigated in mice that underwent trauma-hemorrhage or sham operation. Expressions of endoplasmic reticulum stress proteins Bip, ATF6, PERK, IRE1alpha, and PDI were significantly elevated in the liver after trauma-hemorrhage compared to the controls. The ER stress associated proapoptotic transcription factor CHOP protein expression was also significantly elevated in trauma-hemorrhage group. Consistent with this, enhanced DNA fragmentation was observed, confirming apoptosis, in the liver following trauma-hemorrhage. These results demonstrate the initiation of ER stress and its role in apoptosis and liver injury, subsequent to hemorrhagic trauma.
出血性创伤可导致器官功能障碍、脓毒症和死亡。创伤性出血后，库普弗细胞会异常产生促炎细胞因子，出现组织缺氧和肝损伤。创伤性出血后的生理状况与引发内质网（ER）应激和未折叠蛋白反应所需的因素一致。然而，ER应激对创伤性出血后细胞凋亡和肝损伤的作用尚不清楚。在本研究中，我们对经历创伤性出血或假手术的小鼠的ER应激进行了研究。与对照组相比，创伤性出血后小鼠肝脏中内质网应激蛋白Bip、ATF6、PERK、IRE1α和PDI的表达显著升高。创伤性出血组中，与ER应激相关的促凋亡转录因子CHOP蛋白表达也显著升高。与此一致的是，在创伤性出血后的肝脏中观察到DNA片段化增强，证实了细胞凋亡。这些结果表明，出血性创伤后会引发ER应激，并且其在细胞凋亡和肝损伤中发挥作用。
