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间歇性低氧诱导大鼠心血管损伤及脂联素的保护作用研究

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

作者信息

Jiang Xiufeng, Su Mei, Ding Wenxiao, Ding Ning, Huang Mao, Zhang Xilong

机构信息

Department of Respirology, Wuxi People's Hospital Affiliated With Nanjing Medical University, Nanjing 214194, China.

Email:

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2014 Dec;37(12):888-92.

PMID:25609124
Abstract

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 NO(-)(2)/NO(-)(3) 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 NO(-)(2)/NO(-)(3) level than that in CIH group. Bivariate Correlations showed that NO(-)(2)/NO(-)(3) and eNOS were negatively correlated with systolic blood pressure while heart/body weight ratio, LVEDs, ET-1 and NO(-)(2)/NO(-)(3) 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.

摘要

目的

观察慢性间歇性缺氧(CIH)对大鼠心脏功能和血压的影响,以及脂联素(Ad)的保护作用。

方法

将24只雄性Wistar大鼠随机等分为3组:正常对照组(NC组)、慢性间歇性缺氧组(CIH组)和CIH+Ad组。NC组正常呼吸空气,CIH组和CIH+Ad组进行慢性间歇性缺氧28天。此外,CIH+Ad组大鼠每次静脉注射脂联素20μg,每周1次,连续4周。28天后比较三组的超声心动图、血压、血浆脂联素、内皮素-1(ET-1)和内皮型一氧化氮合酶(eNOS)结果。

结果

HE染色显示CIH大鼠心肌细胞受到CIH损伤。与NC组相比,CIH组大鼠心脏/体重比更大(0.070±0.008对0.057±0.009,P<0.05),收缩压更高[(132±4)对(123±6)mmHg(1mmHg = 0.133kPa),P<0.05],左室射血分数更低[(70.3±4.1)%对(84.1±2.5)%,P<0.05]。与NC组相比,CIH组血浆ET-1升高,而NO(-)(2)/NO(-)(3)和eNOS降低[分别为(26.2±6.9)ng/L对(7.7±2.7)ng/L,(37±9)μmol/L对(65±10)μmol/L,(18±5)μg/L对(27±6)μg/L;P<0.05]。与CIH组相比,CIH+Ad组心脏/体重比、血压和左室射血分数得到改善[0.064±0.009对0.070±0.008,(127±6)mmHg对(132±4)mmHg,P>0.05;(79±7)%对(70±4)%,P<0.05;分别]。CIH+Ad组和CIH组血浆ET-1水平无显著差异,但均显著低于NC组。然而,CIH+Ad组大鼠NO(-)(2)/NO(-)(3)水平高于CIH组。双变量相关性分析显示,NO(-)(2)/NO(-)(3)和eNOS与收缩压呈负相关,而心脏/体重比、左室舒张末期内径、ET-1和NO(-)(2)/NO(-)(3)与左室射血分数呈负相关。

结论

通过氧化应激、ET-1与NO失衡及血管内皮功能受损,CIH可损害大鼠心脏功能,而补充外源性脂联素可改善这些损害。

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