睡眠剥夺上调小鼠胰腺TNF-α的表达

Sleep deprivation up-regulates expression of tumor necrosis factor alpha in mouse pancreas

目的探讨睡眠剥夺对小鼠胰腺形态、功能的影响以及肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)表达变化的病理意义。方法 C57雄性小鼠随机分为正常对照组,睡眠剥夺24 h、48 h和60 h组,观察各组小鼠的精神活动状态及体重变化;检测血清淀粉酶(serum amylase,AMS)水平;采用HE染色和免疫组织化学法观察各组小鼠胰腺的组织学特征及TNF-α表达情况;Western Blot检测TNF-α的表达水平。结果随睡眠剥夺时间的延长,模型组小鼠体重较正常对照组明显下降。AMS水平在睡眠剥夺24 h显著升高,48 h达到峰值后维持至60 h。HE染色可见睡眠剥夺组小鼠出现胰岛细胞排列紊乱、胞质浓缩、细胞间隙扩大;外分泌部细胞酶原颗粒消失,细胞空泡化等病理改变;免疫组化及免疫印迹显示,睡眠剥夺组小鼠胰腺中TNF-α的表达随剥夺时间的延长而明显上调。结论睡眠剥夺后不仅导致小鼠全身衰竭,并通过活化TNF-α而诱导胰腺的炎症反应,导致其形态和功能损伤。

Objective To investigate the impact of sleep deprivation on morphology and function of pancreas in mice and the pathological significance of expression of tumor necrosis factor-α( TNF-α). Methods C57 mice were randomly divided into four groups:control group,and groups with sleep deprivation for 24 h,48 h,60 h,respectively. The mice subjected to sleep deprivation were observed for the general state and changes of body weight; serum amylase( AMS) level was detected. Sectioned Pancreatic slices were observed by H&E staining and immunohistochemical staining to test the histological changes and the expression of TNF-α. Western Blot assay was practiced to detect the expression of TNF-α in the pancreas. Results With the extension of time,the body weight of sleep deprived mice was significantly decreased compared with that of the control group. AMS levels in sleep deprived mice significantly increased at 24 h,reaching the peak at 48 h which lasted till 60 h. H&E staining demonstrated that mice deprived of sleep showed turbid pancreatic islet cells,with cytoplast pyknosis,expansion of interstitial tissue,disappearance of zymogen granules and vacuolization of acinar cells. Immunohistochemistry and Western blot showed that the sleep deprivation groups had increasingly higher expression of TNF-α in the pancreas with the extension of deprivation. Conclusion Sleep deprivation causes systemic failure in mice,and activates TNF-α-induced inflammation of the pancreas,leading to its morphological and functional damage.