慢性间歇低氧对大鼠肝功能的影响及脂联素的保护机制

发布时间：2018-09-14 12:13

【摘要】：目的:近年来,大量研究证实阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome;OSAS)能够导致肝功能的损害。慢性间歇低氧(chronic intermittent hypoxia;CIH)作为OSAS主要的病理生理学特征,可诱发非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)。本研究主要目的是探讨 OS AS 模式CIH对大鼠肝功能的影响及脂联素的保护机制。方法:60只健康雄性6周龄Wistar大鼠(SPF级别,体重180-200g)按随机数字表法分为正常对照组、正常脂联素组、CIH组和CIH +脂联素组各15只。对CIH组和CIH+脂联素组给予每天8小时的CIH,持续处理4个月。同时正常对照组和正常脂联素组大鼠接受正常气压空气处理。正常脂联素组和CIH+脂联素组大鼠接受每周2次脂联素尾静脉注射,每次注射量10μg,为期4个月。造模完成后比较组间血浆天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)水平以及内质网应激(endoplasmic reticulum stress,ERS)和线粒体相关的细胞凋亡状况。结果:正常对照组和正常脂联素组各项观察指标间差异均无统计学意义(均P0.05)。CIH 组 AST 和 ALT 水平[(319±21)和(113±9)U/L]均显著高于正常对照组[(178±19)和(51±9)U/L)]和正常脂联素组[(175±16)和(52±8)U/L](均P0.01)。与正常对照组和正常脂联素组相比,CIH组大鼠肝组织出现较明显的ERS及线粒体相关的细胞凋亡改变。而上述改变在CIH +脂联素组均较CIH组显著减轻(均P0.05)。结论:CIH可以引起大鼠肝功能损伤,脂联素可能通过抑制ERS及线粒体相关凋亡通路而起到保护作用。
[Abstract]:Objective: in recent years, a large number of studies have proved that obstructive sleep apnea syndrome (obstructive sleep apnea syndrome;OSAS) can lead to liver function damage. Chronic intermittent hypoxia (chronic intermittent hypoxia;CIH), as the main pathophysiological feature of OSAS, can induce non-alcoholic fatty liver disease (non-alcoholic fatty liver disease,NAFLD). The aim of this study was to investigate the effects of OS AS CIH on liver function and the protective mechanism of adiponectin in rats. Methods Sixty healthy male 6-week-old Wistar rats (SPF grade, body weight 180-200g) were randomly divided into normal control group, normal adiponectin group (n = 15) and CIH adiponectin group (n = 15). CIH group and CIH adiponectin group were treated with 8 hours CIH, for 4 months. At the same time, normal control group and normal adiponectin group were treated with normal air pressure. Rats in normal adiponectin group and CIH adiponectin group received adiponectin caudal injection twice a week for 4 months. The plasma aspartate aminotransferase (AST),) alanine aminotransferase (ALT) levels, endoplasmic reticulum stress (endoplasmic reticulum stress,ERS) and mitochondrial apoptosis were compared. Results: there was no significant difference between normal adiponectin group and normal adiponectin group (P0.05). The levels of AST and ALT in CIH group [(319 卤21) and (113 卤9) U / L] were significantly higher than those in normal control group [(178 卤19) and (51 卤9) U / L] and normal adiponectin group [(175 卤16) and (52 卤8) U / L] (P0.01). Compared with the normal control group and the normal adiponectin group, there were obvious changes of ERS and mitochondria related apoptosis in the liver tissue of the rats. These changes were significantly reduced in CIH adiponectin group than in CIH group (P0.05). ConclusionCIH can induce liver function injury in rats. Adiponectin may play a protective role by inhibiting ERS and mitochondria related apoptosis pathway.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R766

【参考文献】