间歇性低氧对兔血浆Lp-PLA_2、IL-6和VCAM-1的影响

Effects of Intermittent Hypoxia on Lp-PLA_2,IL-6 and VCAM-1 of Rabbit Plasma

目的建立慢性间歇性低氧新西兰白兔模型,观察和评价间歇性低氧(IH)后对血浆中脂蛋白相关性磷脂酶A2(Lp-PLA2)、白细胞介素6(IL-6)和血管细胞黏附分子1(VCAM-1)的影响及动脉粥样硬化形成情况。方法采用随机对照、前瞻性动物实验和方差分析等方法,建立慢性间歇性低氧新西兰白兔模型。将36只4月龄新西兰大耳白兔随机分为两组:对照组和间歇性低氧组,按照低氧时间4、8、12周,又将对照组和间歇性低氧组各分3组。对照4、8、12周组,每组6只;间歇性低氧4、8、12周组,每组6只。间歇性低氧组置于缺氧舱中给予间歇低氧处理每天8 h。分别于第4周、第8周和第12周给实验兔称重,采静脉血,用ELISA方法检测Lp-PLA2、IL-6和VCAM-1含量,同时取腹主动脉利用HE染色观察动脉粥样硬化形成。结果 (1)间歇性低氧4周组、8周组和12周组两两比较及与对照组比较,血浆中Lp-PLA2、IL-6和VCAM-1表达水平差异有统计学意义(P<0.05),间歇性低氧组与对照组间的差异随时间增加而增大,呈递增趋势,在12周时最明显。(2)对照4周组、8周组和12周组的血浆Lp-PLA2、IL-6和VCAM-1表达水平变化差异无统计学意义。(3)间歇性低氧组的Lp-PLA2、VCAM-1和IL-6血浆表达水平呈现明显正相关性。Lp-PLA2与VCAM-1的相关系数为0.75(P<0.001)。Lp-PLA2与IL-6的相关系数为0.55,(P<0.001)。VCAM-1与IL-6的相关系数为0.76(P<0.001)。(4)间歇性低氧干预下腹主动脉组织HE染色后可观察到动脉粥样硬化的形成。结论慢性间歇性低氧可引起血浆Lp-PLA2、IL-6和VCAM-1水平增高,血浆中IL-6、VCAM-1及Lp-PLA2三者存在相关性,可推测间歇性低氧介导了内皮下炎症因子的聚集导致血管内皮的损伤,进而参与间歇性低氧后动脉粥样硬化的形成。

Aim To observe and evaluate the effect of intermittent hypoxia（ IH） on plasma lipoprotein-associated phospholipase A2（ Lp-PLA2）,interleukin-6（ IL-6） and vascular cell adhesion molecule-1（ VCAM-1） by the rabbit model of chronic intermittent hypoxia and the atherosclerosis formation. Methods Using randomized controlled study,prospective animal,variance analysis and so on. 36 New Zealand White rabbits（ 4 months old） were divided into two groups randomly. According to intermittent hypoxia time at 4,8,12 weeks,intermittent hypoxic group and control group were divided into 3 groups separately. There were 3 groups in the control group（ C1,C2,C3） and the intermittent hypoxia group（ IH1,IH2,IH3）. There were 6 rabbits in each groups. Intermittent hypoxia group were placed in hypoxic chamber to treat by intermittent hypoxia for 8 hours per day. Weighting is at the fourth week,eighth week and twelfth week separately. The content of Lp-PLA2,IL-6 and VCAM-1 was tested by ELISA method. At the same time,the abdominal aorta was stained by HE staining to observe the formation of atherosclerosis. Results（ 1） The plasma levels of Lp-PLA2,IL-6 and VCAM-1 increased as time among IH1,IH2,IH3 and all control groups（ P〈0. 05）,which was the most obvious at 12 th week.（ 2） At the 4th week,8th week and 12 th week,the plasma levels of Lp-PLA2,IL-6 and VCAM-1 had no difference in control groups.（ 3） The plasma levels of Lp-PLA2,IL-6 and VCAM-1 had a positive correlation with each other（ P〈0. 05）. The correlation coefficient was 0. 75,0. 55 and 0. 76 among Lp-PLA2,IL-6 and VCAM-1（ P〈0. 001）.（ 4） The formation of atherosclerosis in aortic tissue can be observed by HE staining after intermittent hypoxia intervention. Conclusion The plasma levels of Lp-PLA2,IL-6 and VCAM-1 was increased by intermittent hypoxia and had a correlation. IH may mediate the aggregation of inflammatory cytokines to lead to vascular endothelial injury and participate the formation of atherosclerosis.