慢性间歇低氧对大鼠心血管系统的影响及脂联素的保护作用

A study on rat cardiovascular injury induced by intermittent hypoxia and the protective role of adiponectin

目的 观察慢性间歇低氧（CIH）对大鼠心功能及血压的影响,探讨脂联素对其保护作用.方法 通过随机数字表法将24只Wistar雄性大鼠分为3组,每组8只,分别为常氧对照组（对照组）、CIH组和CIH-脂联素干预组（干预组）.对照组呼吸正常空气,CIH组和干预组每天行8 h CIH,干预组每周第1天经尾静脉注射脂联素20 μg.比较各组大鼠的超声心动图,血压,血浆脂联素、内皮素-1、内皮型一氧化氮合酶（eNOS）的差异.28 d后处死大鼠,观察各组大鼠心肌细胞结构的改变.结果 与对照组相比,CIH组大鼠心脏与体重比值显著增加（0.070±0.008和0.057±0.009,P＜0.05）,血压显著升高[（132±4）和（123±6）mmHg,l mmHg=0.133 kPa,P＜0.05],左心室射血分数明显降低[（70.3±4.1）％、（84.1±2.5）％,P＜0.05].血浆内皮素-1水平均升高[（26.2±6.9）和（7.7±2.7）ng/L,P＜0.05],NO;/N03[（37±9）和（65±10） μmol/L,P＜0.05]和eNOS水平降低[（18±5）、（27 ±6） μg/L,P＜0.05].干预组大鼠心脏与体重比值,血压,左心室射血分数较CIH组均有所改善,但尚未达到对照组水平.干预组大鼠血浆内皮素-1水平尽管高于对照组,但与CIH组比较差异无统计学意义;NO2-/NO3-水平[（55±10） μmol/L]明显高于CIH组[（37±9） μmol/L,P＜0.05],与CIH组比较差异无统计学意义.相关性分析显示NO2-/NO3-和eNOS水平与收缩压呈负相关;心脏与体重比值、LVED、内皮素-1、NO2-/NO3-与LVEF呈负相关.病理检查结果显示CIH组大鼠心肌细胞损伤明显,细胞肿胀、排列紊乱.结论 CIH可造成大鼠心功能损伤,这种损伤可能通过氧化应激引起血清内皮素-1、NO含量失衡,导致内皮功能障碍,进而损伤心肌有关.而脂联素可能通过减轻氧化应激损伤,改善血管内皮功能,从而减轻间歇低氧造成的心脏损伤.

Objective To observe the effect of chronic intermittent hypoxia （CIH） on rat cardiac function and blood pressure,and the protective role of adiponectin （Ad）.Methods A total of 24 male Wistar rats were randomly and equally divided into 3 groups：normal control group （NC group）,chronic intermittent hypoxygen group （CIH group） and CIH ＋ Ad group.Normal air breathing for NC group and CHI for CIH and CIH ＋ Ad groups were conducted for 28 days.In addition,rats in CIH ＋ Ad group were given intravenous adiponectin at a dosage of 20 μg each time,once a week for successive 4 weeks.The results of echocardiography,blood pressure,plasma adiponectin,endothelin-1 （ET-1） and endothelial nitric oxide synthase （eNOS） were compared among the three groups after 28 days.Results HE stain showed that the myocardial cells of CIH rats were damaged by CIH.Compared with NC group,rats in CIH group presented with a greater heart/body weight ratio （0.070 ± 0.008 vs.0.057 ± 0.009,P 〈 0.05） and systolic blood pressure [（132±4） vs.（123 ±6） mmHg（1 mmHg =0.133 kPa）,P〈0.05] and a lower LVEF [（70.3±4.1）% vs.（84.1 ±2.5）%,P〈0.05].Plasma ET-1 was increased while NO2-/NO3-and eNOS decreased in CIH group,compared with NC group [（26.2 ± 6.9） ng/L vs.（7.7 ± 2.7） ng/L,（37 ±9） μmol/L vs.（65 ± 10） μmol/L,（18 ±5） μg/L vs.（27 ±6） μg/L,respectively; P 〈0.05].The heart/body weight ratio,blood pressure and LVEF were improved in CIH ＋ Ad group compared with those in CIH group [0.064 ± 0.009 vs.0.070 ± 0.008,（127 ± 6） mmHg vs.（132 ± 4） mmHg,P 〉 0.05; （79 ±7）% vs.（70 ±4）%,P 〈0.05; respectively].Plasma ET-1 levels in CIH ＋ Ad and CIH groups showed no significant difference,but were significantly lower in NC group.However,rats in CIH ＋ Ad group had a higher NO2-/NO3-level than that in CIH group.Bivariate Correlations showed that NO2-/NO3-and eNOS were negatively correlated with systolic blood pressure while heart/body weight ratio,LVEDs,ET-1 and NO2-/NO3-were negatively correlated with left ventricular ejection fraction.Conclusions Through xidative stress,ET-1 and NO imbalance and impaired vascular endothelial function,cardiac function could be damaged by CIH in rats,while supplement of extrinsic adiponectin could improve these damages.