慢性间歇低氧对大鼠血清高密度脂蛋白胆固醇和肝脏过氧化物酶体增殖剂激活受体α及三磷腺苷结合盒转运子A1表达的影响

The effect of chronic intermittent hypoxia on serum high-density lipoprotein cholesterol and the expressions of peroxisome proliferators-activated receptors αand adenosine triphosphate binding cassette transporter A1 in rat liver tissues

目的探讨慢性间歇性低氧对大鼠血清高密度脂蛋白胆固醇（HDL—C）及相关代谢指标过氧化物酶体增殖剂激活受体（PPAR）α、三磷腺苷结合盒转运子A1（ABCA1）的影响。方法建立慢性间歇低氧（CIH）大鼠模型，数字抽签随机分为6组，分别为3周对照组、6周对照组、3周10％CIH组、3周5％CIH组、6周10％CIH复氧组和6周5％CIH复氧组（即在给予10％或5％CIH处理3周后转为常氧饲养3周）。比较各组HDL-C差异，观察各组大鼠肝组织形态改变，比较各组大鼠肝脏PPARd、ABCA1表达情况。结果CIH干预大鼠血TC、TG、LDLC水平较对照组升高，复氧大鼠血TC、TG、LDL-C水平较CIH干预大鼠降低，与相应对照组差异无统计学意义（均P〉0．05）。CIH干预大鼠血清HDL-C水平较对照组降低，复氧后大鼠血HDL-C水平较CIH干预大鼠升高，与相应对照组比较差异无统计学意义（均P〉0．05）。CIH干预大鼠PPARd、ABCA1较对照组降低；复氧后大鼠PPARα、ABCA1较CIH干预大鼠升高，复氧大鼠与相应对照组比较，PPARa、ABCA1差异无统计学意义（均P〉0．05），恢复至常氧水平。结论阻塞性睡眠呼吸暂停综合征（OSAHs）模式的CIH大鼠模型血清HDL-C降低，复氧干预后可有效提高HDL-C水平；OSAHS模式的CIH大鼠模型可能通过PPARa—ABCA1通路导致HDL—C紊乱，复氧3周干预治疗可有效使大鼠PPARα、ABCA1表达水平恢复至常氧水平，从而逆转血脂紊乱。

Objective To investigate the effect of chronic intermittent hypoxia（CIH）on serum high-density lipoprotein eholesterol（HDL-C）and the changes of HDL-C metabolism-related inclieators such as the expressions of peroxisome proliferators-aetivated receptorα （PPARα）and adenosine triphosphate binding cassette transporterAl（ABCA1）in liver in male SD rats. Methods Obstructive sleep apnea syndrome（OSAHS）-induced CIH rats were randomly allocated into 6 groups： 10% CIH-3 weeks,50%CIH-3 weeks,5 %CIH-3 week＋RH（Removal of hypoxia-3 weeks）,10%CIH 3 weeks α- RH（Removal of hypoxia-3 weeks）, control group-3 weeks, and control group-6 weeks. Serum lipids were measured and compared. To observe and compare the liver pathology, the expression levels of PPARα and ABCA1 in liver tissue of CIH rats were detected by immunohistochemical method. Results The levels of serum TC,TG and LDL-C was significantly higher in CIH rats than in control group. The levels of TC,TG and LDL-C were significantly lower in reoxygenation groups than in CIH groups. There was no significant difference between experiment groups and correspondent controlgroups（all P〈0.05）. Compared with control group,CIH rats had significantly lower levels of serum HDL-C^Compared with CIH groups, the levels of HDL-C were significantly higher in reoxygenation groups. There was no significant difference between experiment groups and correspondent control groups（all P〈0.05）. Compared with control group, the expression of PPARa and ABCA1 of CIH group was significantly lower;Compared with CIH groups, the expression of PPARαand ABCA1 was significantly higher in reoxygenation groups ; There was no significant difference in the expression of PPARα and ABCA1 between reoxygenation groups and correspondent control groups, in which the oxygen level was recovered to normal. Conclusions The serum HDL C level was obviously decreased in OSAHS-induced CIH rats, and the decreased serum HDL-C can be effectively improved by reoxygenation intervention. OSAHS-induced CIH may lead to the dyslipidemia through PPARα-ABCA1 pathway,and reoxygenation intervention for three weeks can effectively recover the expression levels of PPARa and ABCA1 to normal levels, which suggests that if CIH is effectively intervented, the change of PPARαand ABCA1 of liver can be reversed, thereby reversing dyslipidemia.