摘要
目的探讨高迁移率族B1(high mobility group B1,HMGB1)蛋白在创伤引起大鼠肺组织内质网应激(endoplasmic reticulum stress,ERS)变化中的作用。方法用标准重物挤压大鼠双后肢建立创伤应激致大鼠急性肺损伤模型。第一部分实验将大鼠随机分为体位对照组和挤压后6 h、18 h和30 h组,第二部分实验分为体位对照组、挤压后18 h组、HMGB1抑制剂正丁酸钠组和挤压后18 h+抑制剂组。用蛋白质印迹法检测肺组织HMGB1以及ERS相关蛋白(GRP78、caspase-12、CHOP和IRE1α)的表达变化。同时,常规HE染色观察肺组织病理学改变。结果与体位对照组比较,挤压大鼠后肢可引起肺组织中ERS相关蛋白(GRP78、caspase-12、CHOP和IRE1α)以及HMGB1蛋白表达明显增高,挤压后30 h时上述蛋白表达降低但仍高于体位对照组,同时大鼠出现明显肺损伤病理变化。与挤压后18 h组比较,挤压后18 h+抑制剂组大鼠肺组织中上述ERS相关蛋白及HMGB1蛋白表达降低,大鼠肺损伤病理变化减轻。结论创伤应激能启动HMGB1-ERS通路导致大鼠急性肺损伤。
Objective To explore the role of high mobility group B1(HMGB1)protein in the post-traumatic endoplasmic reticulum stress(ERS)in rat lung tissues.Methods The rat model of acute lung injury was established by crushing the hind limbs of rats with standard weight.The first experiment was to divide rats into postural control group and crush groups(6 h,18 h and 30 h after crushing).The second experiment was to divide rats into postural control group,18 h crush group,HMGB1 inhibitor sodium butyrate(SB)group and 18 h crush+SB group.The protein expression changes of HMGB1 and ERS-related proteins(GRP78,caspase-12,CHOP and IRE1α)in rat lung tissues were detected with Western blotting.Meanwhile,the pathological changes of rat lungs were observed by HE stain.Results Compared with the postural control group,the expression levels of ERS-related proteins(GRP78,caspase-12,CHOP and IRE1α)and HMGB1 protein in rat lung tissues by crushing the hind limbs of rats were obviously increased.The protein levels reduced at 30 h after crushing but were still higher than those of postural control group and obvious pathological changes of acute lung injury were observed simultaneously in rats.Compared with the 18 h crush group,the expression levels of the ERS-related proteins and HMGB1 protein in rat lung tissues were attenuated in 18 h crush+SB group,and the pathological changes of rat lung injury began to alleviate.Conclusion HMGB1-ERS pathway activated by traumatic stress can lead to acute lung injury in rats.
作者
陆建锋
张庆婕
李雪豪
刘国庆
刘夷嫦
谷振勇
LU Jian-feng;ZHANG Qing-jie;LI Xue-hao;LIU Guo-qing;LIU Yi-chang;GU Zhen-yong(Department of Forensic Medicine,Medical College of Nantong University,Nantong 226001,China)
出处
《法医学杂志》
CAS
CSCD
2018年第4期347-351,共5页
Journal of Forensic Medicine
基金
国家自然科学基金资助项目(81273341)
江苏省高校优势学科建设工程资助项目(PAPD)
关键词
法医病理学
挤压伤
内质网应激
高迁移率族蛋白质类
肺
大鼠
forensic pathology
crush injury
endoplasmic reticulum stress
high mobility group proteins
lung
rats
