Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.
Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.
复制标题
脂联素通过抑制内质网应激保护大鼠心肌免受慢性间歇性缺氧引起的损伤
DOI：
10.1371/journal.pone.0094545
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Ding W;Zhang X;Huang H;Ding N;Zhang S;Hutchinson SZ;Zhang X
阻塞性睡眠呼吸暂停综合征（OSAS）与心衰、高血压、动脉粥样硬化、心律失常等多种心血管疾病有关。在许多相关因素中，慢性间歇性缺氧（CIH）是OSAS的主要因素。为了评估CIH对OSAS继发性心功能的影响，我们建立了Wistar大鼠模型研究CIH对OSAS继发性心功能的影响。具体来说，我们研究了缺氧组织损伤的潜在细胞机制以及脂联素对缺氧损伤的可能保护作用。在第一治疗组，大鼠暴露于CIH条件下（最低点O2, 5 - 6%） 8小时/天，持续5周。随后用超声心动图测量cih诱导的心功能障碍。与正常对照组（NC）相比，暴露组大鼠左室收缩末尺寸和收缩末容积升高，左室射血分数和左室缩短分数降低（p<0.05）。然而，在CIH + Ad组添加脂联素（Ad）后，我们看到上述左心室功能升高有所缓解（p<0.05）。为了评估危重心脏损伤，我们通过末端脱氧核苷酸转移介导的dUTP缺口末端标记（TUNEL）分析检测心肌凋亡。结果表明，CIH组细胞凋亡率（2.948%）显著高于NC组（0.4167%）和CIH + Ad组（1.219%）（p<0.05）。cleaved- caspase-3、cleaved- caspase-9和cleaved-caspase-12的蛋白表达与我们的TUNEL结果一致（p<0.05）。从机制上讲，我们的研究结果表明，在CIH条件下，内质网应激下表达的蛋白质和活性氧（ROS）的表达显著升高，而补充Ad则部分降低了它们。总的来说，我们的研究结果表明，Ad增强可以通过抑制ros依赖性内质网应激来改善cih诱导的左心室功能障碍和相关的心肌凋亡。
Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5–6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.
登录
查看更多内容
影响因子：
8.7
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
DOI：
10.1164/rccm.200504-560oc
发表时间：
2005-10-01
影响因子：
24.7
作者：
Chen, L;Einbinder, E;Scharf, SM
通讯作者：
Scharf, SM
DOI：
10.1016/s0022-2828(08)80028-4
发表时间：
1995-01-01
影响因子：
5
作者：
BELTRAMI, CA;FINATO, N;ANVERSA, P
通讯作者：
ANVERSA, P
DOI：
10.1152/ajpheart.00783.2002
发表时间：
2003-06-01
影响因子：
4.8
作者：
Hochhauser, E;Kivity, S;Vidne, BA
通讯作者：
Vidne, BA
DOI：
10.1007/s00399-011-0164-8
发表时间：
2012-03-01
期刊：
Herzschrittmachertherapie & Elektrophysiologie
影响因子：
--
作者：
Bitter, T;Korber, B;Oldenburg, O
通讯作者：
Oldenburg, O