Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease.
Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease.
复制标题
草原田鼠的长期社会隔离会导致内皮功能障碍：对抑郁症和心血管疾病的影响。
DOI：
10.1016/j.physbeh.2012.03.019
复制
发表时间：
2012
影响因子：
2.9
通讯作者：
Grippo,AngelaJ
中科院分区：
文献类型：
--
作者：
Peuler,JacobD;Scotti,Melissa-AnnL;Phelps,LauraE;McNeal,Neal;Grippo,AngelaJ
抑郁症患者的内皮依赖性血管舒张功能受损;最近的一个证据是老年抑郁症患者的肾上腺素能预收缩小动脉活检中乙酰胆碱（ACh）诱导的舒张减少。一般来说，ACh的此类使用结果已被验证为内皮相关心血管疾病的最具预测性的标志物。因此，我们研究了社会隔离的草原田鼠（一种与人类抑郁症和心血管疾病相关的新动物模型）对ACh的血管反应性。在一个月的社会隔离（与兄弟姐妹配对）后，从雌性草原田鼠身上仔细解剖了胸腹。仅对肾上腺素能药物苯肾上腺素（PE）收缩然后ACh松弛的动脉瘤进行评价。其中，乙酰胆碱诱导的舒张显著减少社会隔离（p<0.05），最大舒张仅达到30%（PE诱导的预收缩），而配对（对照）动物的舒张达到47%。实验去除内皮细胞从一个额外的组主动脉组织废除所有ACh松弛，包括差异。在这些相同的组织中，最大有效浓度的一氧化氮供体硝普钠仍然完全放松所有PE诱导的无内皮平滑肌的预收缩，并在相同程度上在组织中从隔离与配对动物。最后，在没有PE诱导的预收缩的情况下，ACh并不松弛而是收缩主动脉组织，并且如果内皮完整，则在来自社会隔离动物的组织中的收缩程度显著更大（p<0.05）。因此，草原田鼠的社会隔离可能1）损害保护性抗动脉粥样硬化因子如一氧化氮从血管内皮的正常释放（而不改变血管平滑肌对这些因子的固有反应性）和2）导致内皮释放收缩因子。据我们所知，这是第一次在完全由社会孤立引起的抑郁症动物模型中证明这种现象。这些发现对于理解抑郁症和心血管疾病的机制具有重要意义。
Humans with depression show impaired endothelium-dependent vasodilation; one recent demonstration of which was in the form of a reduced acetylcholine (ACh)-induced relaxation of adrenergically-precontracted small arteries biopsied from older depressed patients. Results from such uses of ACh in general have been validated as the most predictive marker of endothelium-related cardiovascular diseases. Accordingly, we examined vascular reactivity to ACh in the socially isolated prairie vole, a new animal model relevant to human depression and cardiovascular disease. Thoracic aortas were carefully dissected from female prairie voles after one month of social isolation (versus pairing with a sibling). Only aortas that contracted to the adrenergic agent phenylephrine (PE) and then relaxed to ACh were evaluated. Among those, ACh-induced relaxations were significantly reduced by social isolation (p<0.05), with maximum relaxation reaching only 30% (of PE-induced precontraction) compared to 47% in aortas from paired (control) animals. Experimental removal of the endothelium from an additional set of aortic tissues abolished all ACh relaxations including that difference. In these same tissues, maximally-effective concentrations of the nitric oxide-donor nitroprusside still completely relaxed all PE-induced precontraction of the endothelial-free smooth muscle, and to the same degree in tissues from isolated versus paired animals. Finally, in the absence of PE-induced precontraction ACh did not relax but rather contracted aortic tissues, and to a significantly greater extent in tissues from socially isolated animals if the endothelium was intact (p<0.05). Thus, social isolation in the prairie vole may 1) impair normal release of protective anti-atherosclerotic factors like nitric oxide from the vascular endothelium (without altering the inherent responsiveness of the vascular smooth muscle to such factors) and 2) cause the endothelium to release contracting factors. To our knowledge this is the first demonstration of this phenomenon in an animal model of depression induced solely by social isolation. These findings have implications for understanding mechanisms involved in depression and cardiovascular disease.