摘要
目的研究褪黑素对miRNA-223表达的影响及对脓毒症小鼠心肌损伤保护的作用机制。方法取48只健康雄性C57BL/6小鼠,按随机数字表法分为假伤组、生理盐水组及褪黑素治疗组,每组16只。生理盐水组和褪黑素治疗组采用腹腔注射内毒素制备脓毒症模型,褪黑素治疗组于建模前30 min、建模时、伤后4 h分3次注射褪黑素,生理盐水组和假伤组在褪黑素治疗组相应给药时间点注射等量生理盐水。内毒素处理24 h后,3组均取8只小鼠,收集血液,检测血清中白介素(IL)-1β、IL-6含量,蛋白免疫印迹法检测Bcl-2、Bax蛋白表达; 48 h后处死其余小鼠,收集心肌组织,检测miRNA-223含量。结果褪黑素治疗组、生理盐水组血清IL-1β、IL-6水平高于假伤组,褪黑素治疗组低于生理盐水组(P <0. 01)。褪黑素治疗组、生理盐水组Bcl-2表达水平低于假伤组,褪黑素治疗组高于生理盐水组(P <0. 01);褪黑素治疗组、生理盐水组Bax蛋白表达水平高于假伤组,褪黑素治疗组低于生理盐水组(P <0. 01)。与假伤组比较,生理盐水组心肌纤维明显肿胀,大量炎性细胞浸润,褪黑素治疗组心肌结构则较生理盐水组明显改善。褪黑素治疗组、生理盐水组心肌组织miRNA-223水平均低于假伤组,褪黑素治疗组高于生理盐水组(P <0. 01)。结论褪黑素可能通过上调心肌组织miRNA-223的表达,减少IL-1β、IL-6等炎性因子的释放,抑制炎性反应,从而减少心肌组织的凋亡,保护心肌组织。
Objective To study effect of melatonin （MT） on miRNA-223 expression and its protective mecha- nism for myocardial injury in mice with sepsis. Methods A total of 48 healthy male C57BL/6 mice were divided into sham injury group, physiological saline （PS） group and MT group （n = 16 for each group） according to random digits table methods. PS and MT groups were injected intraperitoneally with endotoxin to establish septic models. MT group was injected with melatonin at 30 rain before modeling, at the time of modeling and at 4 h after modeling, while PS group and sham injury group were injected with the same volumes of physiological saline at the corresponding time point of adminis- tration in MT group. At 24 h after endotoxin treatment, 8 mice in each group were taken off for blood collected, and then serum levels of interleukin-1β（ IL-1 β） and IL-6 were detected, and Bel-2 and Bax protein expressions were detected by western blotting. The rest of the mice were killed 48 h later, and myocardial tissues were collected to detect miRNA-223 content. Results Serum IL-1β and IL-6 levels in MT and PS groups were significantly higher than those in sham injury group, while the levels in MT group w-ere significantly lower than those in PS group （P 〈 0. 01 ）. Bcl-2 expressions in MT and PS groups were significantly lower than that in sham injury group, and the expression in MT group was significantly higher than that in PS group （P 〈 0.01 ）. Bax protein expressions in MT and PS groups were significantly higher than thatin sham injury group, and the expression in MT group was significantly lower than that in PS group （P 〈 0.01 ）. Compared with those in sham injury group, myocardial fibers were obviously swollen, and a large number of inflammatory cells were infiltrated in PS group. Myocardial structure was significantly better in MT group than that in PS group. The mieroR- NA-223 levels in myocardial tissues in MT and PS groups were significantly lower than that in sham injury group, while the level in MT group was significantly higher than that in PS group （P 〈 0.01 ）. Conclusion Melatonin may inhibit inflammatory reaction by up-regulating miRNA-223 expression in myocardial tissues and reducing release of inflammatory factors such as IL-1β and IL-6 in order to decrease apoptosis of myocardial tissues and protect myocardial tissues.
作者
刘铭传
李林成
曹梦远
张家宁
刘洋
何亭
LIU Ming-chuan1 , LI Lin-cheng1 , CAO Meng-yuan a , ZHANG Jia-ning1 , LIU Yang b , HE Ting b(1. The Fourth Bri- gade, Basic Medicine College of Medical University of PLA Air Force, Xi＇an 710032, China; a. Emergency Department, Xijing Hospital, b. Department of Burns and Cutaneous Surgery, 2. Xijing Hospital Affiliated to Medical University of PLA Air Force, Xi＇an 710032, China)
出处
《解放军医药杂志》
CAS
2018年第10期1-5,共5页
Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
基金
国家自然科学基金青年科学基金项目(81601689
81501666)
空军军医大学西京医院学科助推计划研究探索项目(XJZT15M11)
