[慢性间歇性缺氧对大鼠肝脏脂质代谢的影响及Tempol的干预作用]

[Impact of chronic intermittent hypoxia upon rat liver lipid metabolism and interventional effect of Tempol].

作者信息

Zhao Hai-yan, Chen Bao-yuan, Guo Run, Kong Cheng-ying, Wan Nan-sheng, Zhang Jing

机构信息

Department of Respiratory Medicine, Tianjin Medical University, Tianjin, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2013 Feb 5;93(6):407-10.

PMID:23660256

Abstract

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 triglyceride (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 in IA group ((20.3 ± 3.1), (18.7 ± 1.3) U/L) and CG 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 IH 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 ADP increased and changed more obviously when early intervention was applied (all P < 0.01).

CONCLUSIONS

CIH causes the morphologic changes of liver and the elevations of ALT and AST, but results not in lipid deposition in liver cells. Anti-oxidation of Tempol can block intermittent hypoxia associated with liver injury.

摘要

目的

探讨慢性间歇性缺氧（CIH）对大鼠肝脏脂质代谢的影响及抗氧化剂Tempol的作用。

方法

将80只雄性Wistar大鼠随机分为间歇性缺氧组（10、20、30、40次/小时）、间歇性缺氧Tempol治疗组、间歇性缺氧生理盐水治疗组、间歇性空气模拟组（IA）和空白对照组（CG）。取肝脏组织切片进行苏木精-伊红染色。检测血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平。检测肝脏匀浆甘油三酯（TG）、总胆固醇（TC）、游离脂肪酸（FFA）以及血清TG、TC、脂联素（ADP）水平。

结果

肝脏组织学：间歇性缺氧组表现为肝细胞肿胀、核染色质增多、肝细胞膜破坏。随着频率增加，出现局部坏死及炎性细胞浸润。但未见脂肪变性。Tempol早期治疗组和IA组未见肝细胞肿胀或炎性细胞浸润。间歇性缺氧组中，ALT和AST活性随频率增加而升高（均P<0.01）。间歇性缺氧组ALT和AST水平[（48.6±3.6），（25.4±2.6）U/L]高于IA组[（20.3±3.1），（18.7±1.3）U/L]和CG组[（17.5±2.4），（1’8.8±1.3）U/L]（均P<0.01）。在Tempol治疗组降低，早期干预时更明显（均P<0.01）。肝脏匀浆TG、TC和FFA在间歇性缺氧组、IA组和CG组间无差异（均P>0.05），间歇性缺氧组不同频率间也无差异（均P>0.05）。间歇性缺氧组血清TG、TC水平高于IA组和CG组，而ADP水平较低（均P<0.01）。间歇性缺氧组不同频率间变化更明显（均P<0.01）。在Tempol治疗组，血清TG、TC降低而ADP升高，早期干预时变化更明显（均P<0.01）。