慢性间歇低氧对大鼠肝功能的影响及脂联素的保护机制

Effects of chronic intermittent hypoxia on hepatic function and protective mechanism of adiponectin in rats

目的探讨慢性间歇低氧（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Wistar大鼠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。CIH组和CIH＋脂联素组每天行8h的CIH，为期4个月。正常对照组和正常脂联素组大鼠同时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。实验结束时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（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P〉0．05）。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P〈0．05）。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CIH＋脂联素组上述改变均较CIH组减轻（均P〈0．05）。结论CIH可以引起大鼠肝脏损伤，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。

Objective To explore the effect of chronic intermittent hypoxia （CIH） on rats hepatic function, and the protective mechanism of adiponectin （Ad）. Methods Sixty healthy male wistar rats were randomly divided into 4 groups ： normal control （ NC）, NC ＋ Ad, CIH, and CIH ＋ Ad groups with 15 rats in each. The rats in CIH and CIH ＋ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC ＋ Ad groups were housed with normal pressure air. The rats in the NC ＋ Ad and CIH ＋ Ad groups were additionally treated with an intravenous injection of Ad （10μg）, twice a week for 4 months. At the end of experiment, comparison among groups was made about plasma levels of aspartate amino transferase （AST）, alanine amino transferase （ALT）, degrees of endoplasmic reticulum stress （ERS） and mitochondrium associated cellular apoptosis. Results No significant difference was detected in all items between NC and NC ＋ Ad groups （ all P 〉 0. 05）. Plasma hepatic enzyme levels of AST and ALT were significantly higher in CIH group [ （319 ± 21 ） and （ 113 ± 9 ） U/L] than those inNC group [（178 ±19） and （51±9） U/L] and NC＋Ad group [（175±16） and （52±8） U/L] （all P 〈0. 05）. Compared NC with NC ＋ Ad group, there was more remarkable ERS and mitochondrial injury associated cellular apoptosis in hepatic tissues of CIH group. Such pathological changes were less obvious in CIH ＋ Ad group than in CIH group （ all P 〈 0. 05 ）. Conclusion CIH can induce hepatic injury in rats, while Ad supplement may play a protective role possibly through inhibition of ERS and associated pathways of cellular apoptosis.