内质网应激诱导的细胞凋亡在大鼠压疮深部组织损伤中的作用  

The role of cell apoptosis mediated by endoplasmic reticulum stress( ERS) of deep tissue injury of pressure ulcer of rats

作　　者：潘莹莹[1] 徐洁[2] 王晓慧[1] 毛挺挺 谢浩煌[1] 张宏宇[3] 肖健[3] 李校堃[3] 姜丽萍[1] 

机构地区：[1]温州医科大学护理学院 [2]温州医科大学附属第一医院胸外科 [3]温州医科大学药学院,浙江温州325035

出　　处：《中国应用生理学杂志》2015年第5期396-400,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(81372064)

摘　　要：目的:观察压疮大鼠深部组织损伤(DTI)中肌细胞内质网应激(ERS)相关因子表达的变化,探讨内质网应激诱导的细胞凋亡在压疮深部组织损伤中的作用。方法:健康雄性SD大鼠50只,随机分为正常(Con)组,模型(Model)组,实验组(生理盐水(NS)组与4-苯基丁酸(PBA)组),实验组按观察时间点又分为4 d,7 d,14 d,21 d四组(n=5)。PBA组于造模结束后2 ml生理盐水溶解PBA灌胃,隔天1次;NS组予等量生理盐水灌胃。于各时间点处死动物,收集受压肌肉组织。HE染色观察肌肉组织病理变化;TUENL染色观察细胞凋亡;免疫组化检测ERS分子葡萄糖调节蛋白78(GRP78)、C/EBP(CHOP)、凋亡酶12(Caspase 12)的水平。结果:HE染色显示与Con组相比,各实验组肌肉组织出现不同程度病理退化表现,PBA组与NS组相比,损伤程度有所缓解,新生肌纤维融合更快;TUNEL结果显示受压各组较正常组细胞凋亡数增加,于4 d达到高峰,以后逐渐下降,PBA干预后细胞凋亡有所减少(P<0.05);免疫组化结果显示:肌肉组织NS组GRP78、CHOP、Caspase 12蛋白表达在4 d达到高峰后逐渐下降。NS组各蛋白在各时间点表达均明显高于PBA组(P<0.05)。结论:内质网应激诱导的细胞凋亡参与压疮深部组织损伤病理进程,其相关机制可能与CHOP、Caspase 12介导的的细胞凋亡有关。Objective： To observe the the expression of endoplasmic reticulum stress （ERS） related factors in deep tissue injury （DTI） at pressure ulcer rat and to investigate the ERS mechanism of DTI in muscle tissue and protective effect of 4- phenylbutyrie acid （4-PBA） in local tissue. Methods： Fifty male SD rats were randomly devided into control group, model group, experimental group NS group and PBA group, the experimental groups were divided into 4 d, 7 d, 14 d and 21 d group according to the observation time （ n = 5）. Rats in the PBA group were administrated with gastric perfusion of 4-PBA after the modeling; the NS group was given normal saline of the same quantity. Using HE staining to observe morphologic character. The expression of glucose regulated protein 78（ GRP78）, CHOP, Caspase 12 were detected by im- munohistochemical staining. Cell apoptosis was detected by TUNEL assay. Results： HE staining results showed that each group demonstrated compression injury compared with control group： cellular swelling, ompaction of nuclear, and apoptosis in muscle tissue. The new muscle fiber in 4-PBA group fused faster than those in NS group. The number of TUNEL positive cells peaked at 4 day after compression, then got de- creased on day 7 in muscle tissue, apoptosis positive cells were diminished after 4-PBA treatment. The immunohistechemieal staining results showed that the expression of protein GRP78, CHOP, Caspase 12 peakd 4 d after modeling and decreased gradually. The GRP78, CHOP, Caspase 12 protein expression were significantly higher than those of PBA group at all time points （ P 〈 0.05）. Conclusion： Cell apoptosis in- duced by endoplasmic retieulum stress took part in deep tissue injury resulting of pressure ulcer, which mechanism might be related to reducing apoptosis mediated by CHOP, Caspase 12.

关 键 词：内质网应激 细胞凋亡 压疮 深部组织损伤 4-苯基丁酸 大鼠 

分 类 号：R632.1[医药卫生—外科学]