Habib Mohamed, Shaker Safaa, El-Gayar Nesreen, Aboul-Fotouh Sawsan
Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
PLoS One. 2015 Mar 31;10(3):e0120559. doi: 10.1371/journal.pone.0120559. eCollection 2015.
Several studies reveal that diabetes doubles the odds of comorbid depression with evidence of a pro-inflammatory state underlying its vascular complications. Indeed, little information is available about vascular effects of antidepressant drugs in diabetes.
We investigated the effect of chronic administration of fluoxetine "FLU" and imipramine "IMIP" on behavioral, metabolic and vascular abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).
Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP in a comparable manner. Diabetic and non-diabetic rats exposed to CRS exhibited abnormalities in glucose homeostasis, lipid profile and vascular function, manifested by decreased endothelium-dependent relaxation, increased systolic blood pressure and histopathological atherosclerotic changes. Vascular and metabolic dysfunctions were associated with significant increase in aortic expression of TLR-4, and pro-inflammatory cytokines (TNF-α and IL-1ß). FLU ameliorated these metabolic, vascular and inflammatory abnormalities, while IMIP induced either no change or even worsening of some parameters.
FLU has favorable effect over IMIP on metabolic, vascular and inflammatory aberrations associated with DM and CRS in Wistar rats, clarifying the preference of FLU over IMIP in management of comorbid depression in diabetic subjects.
多项研究表明，糖尿病使共病抑郁症的几率翻倍，有证据显示其血管并发症存在促炎状态。实际上，关于抗抑郁药物在糖尿病中的血管作用的信息很少。
我们研究了慢性给予氟西汀（“FLU”）和丙咪嗪（“IMIP”）对暴露于慢性束缚应激（CRS）的糖尿病和非糖尿病大鼠的行为、代谢和血管异常的影响。
糖尿病和CRS均诱发了抑郁样行为，在糖尿病/抑郁大鼠中更为明显；氟西汀和丙咪嗪的慢性治疗以类似方式逆转了这种行为。暴露于CRS的糖尿病和非糖尿病大鼠在葡萄糖稳态、血脂谱和血管功能方面表现出异常，表现为内皮依赖性舒张降低、收缩压升高和组织病理学动脉粥样硬化改变。血管和代谢功能障碍与主动脉中TLR-4以及促炎细胞因子（TNF-α和IL-1β）的表达显著增加有关。氟西汀改善了这些代谢、血管和炎症异常，而丙咪嗪要么没有变化，甚至使一些参数恶化。
在Wistar大鼠中，氟西汀在与糖尿病和CRS相关的代谢、血管和炎症异常方面比丙咪嗪具有更有利的作用，这阐明了在糖尿病患者共病抑郁症的管理中氟西汀比丙咪嗪更受青睐的原因。
