目的探讨慢性间歇低氧对普通大鼠肝脏脂质代谢的影响及抗氧化剂Tempol的干预作用。方法成年雄性Wistar大鼠80只,分为不同频率(10、20、30、40次/h)间歇低氧组、Tempol干预组、生理盐水干预组、间歇正常氧组、空白对照组。低氧暴露时间为每日9:00-17:00,共6周。暴露结束后,肝组织HE染色观察形态学,酶比色法测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,化学比色法测定肝匀浆甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)水平及血清TG、TC、脂联素(ADP)水平。结果间歇低氧各组肝细胞肿胀,胞核染色加深,核膜增厚,随频率增加出现肝细胞局灶性坏死,炎性细胞浸润,但未出现肝细胞脂质含量增多及脂肪变性;间歇正常氧组及Tempol早期干预组无细胞水肿或炎性细胞浸润。随频率增加间歇低氧组血清ALT、AST活性增加(均P〈0.01);间歇低氧组ALT、AST水平[(48.6±3.6)、(25.4±2.6)U/L]显著高于间歇正常氧组[(20.3±3.1)、(18.74±1.3)U/L]和空白对照组[(17.5±2.4)、(18.8±1.3)U/L](均P〈0.01);Tempo/干预组肝酶水平降低,且干预越早降低越明显(均P〈0.01)。不同频率间歇低氧组肝匀浆TG、TC和FFA水平差异均无统计学意义(均P〉0.05);间歇低氧组与间歇正常氧组及空白对照组比较,肝匀浆中TG、TC和FFA水平差异亦均无统计学意义(均P〉0.05)。间歇低氧组血清TG、TC水平显著高于间歇正常氧组及空白对照组(均P〈0.01),但ADP水平显著低于该2组(均P〈0.01);且随频率的增加变化更加显著;Tempol干预组血清TG、TC降低,ADP升高,干预越早变化越明显(均P〈0。01)。结论慢性间歇低氧能造成非肥胖大鼠肝脏形态学改变及肝酶升高,但单纯间歇低氧没有使肝脏脂肪堆积的作用;Tempol?
Objective To explore the impact of chronic intermittent hypoxia (CIH) upon rat liver lipid metabolism and effect of anti-oxidant Tempol. Methods Male Wistar rats ( n = 80) were randomly divided into intermittent hypoxia group (10, 20, 30, 40 times/h), intermittent hypoxia Tempol treatment group, intermittent hypoxia normal saline treatment group, intermittent air mimic group (IA) and blank control group (CG). Sections of liver were stained with hematoxylin and eosin. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Levels of liver homogenate triglyeeride (TG), total cholesterol (TC), free fatty acids (FFA) and serum TG, TC, adiponectin (ADP) were measured. Results Liver histology: IH group exhibited hepatocellular swelling, hyperchromatosis, disrupted hepatocellular membrane. With the increase of frequency, there were local necrosis and infiltration of inflammatory cells. But no steatosis was seen. Tempol early treatment and IA groups exhibited no hepatocellular swelling or inflammatory cell infiltration. The activities of ALT and AST increased along with the increased frequency in IH group ( all P 〈 0. 01 ). The levels of ALT and AST in IH group ( ( 48.6 ± 3.6), (25.4±2.6)U/L) were higher than those inlA group ((20.3 ±3.1), (18.7±1.3) U/L) andCG group ( ( 17.5 ±2.4), ( 18.8 ± 1.3) U/L) ( all P 〈 0. 01 ). It decreased in Tempol treatment group, and more obviously when early intervention was applied ( all P 〈 0. 01 ). Liver homogenate TG, TC and FFA had no difference among IH, IA and CG groups ( all P 〉 0. 05 ) , and no difference in different frequencies in 1H group (all P 〉 0. 05). The levels of serum TG, TC in IH groups were higher than those in IA and CG groups while ADP was lower ( all P 〈0. 01 ). It changed more obviously in different frequencies in IH group (all P 〈0. 01 ). In Tempol treatment group, serum TG, TC decreased while A