氯沙坦对慢性不可预知温和应激模型大鼠的抗抑郁作用

目的探讨氯沙坦（Los）对慢性不可预知温和应激（CUMS）模型大鼠抑郁行为的影响，对其抗炎和抗氧化作用进行考察，探究其潜在的抗抑郁机制。 方法将24只SD大鼠随机分为4组：对照组（Control）、氯沙坦组（Los）、抑郁组（CUMS）、抑郁+氯沙坦组（CUMS+ Los），每组6只。Los组、CUMS+Los组每天灌胃10 mg/kg的Los溶液，Control组和CUMS组每日灌胃等体积的生理盐水，连续8周。采用糖水偏好实验、强迫游泳实验和高架十字迷宫实验评估大鼠抑郁样行为。酶联免疫吸附法检测大鼠海马的血管紧张素Ⅱ（Ang Ⅱ）的含量。荧光定量PCR检测血管紧张素Ⅱ1型受体（AT1R）和炎性因子白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）的表达量。分光光度法检测海马的超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量。 结果Los组较Control组糖水的消耗量、进入开放臂的时间、进入开放臂次数以及比率、强迫游泳不动时间、Ang Ⅱ含量、AT1R、IL-6、TNF-α表达量、SOD活性、MDA含量差异均无统计学意义（P>0.05）。CUMS组较Control组糖水的消耗量、进入开放臂的时间、进入开放臂次数以及比率、SOD活性显著降低，强迫游泳不动时间、Ang Ⅱ含量和AT1R、IL-6、TNF-α表达量及MDA含量显著升高，差异具有统计学意义（P<0.05）。CUMS+Los组较CUMS组糖水的消耗量、进入开放臂的时间、进入开放臂次数以及比率、SOD活性均升高，而强迫游泳不动时间、Ang Ⅱ含量和AT1R、IL-6、TNF-α表达量及MDA含量均降低，差异均具有统计学意义（P<0.05）。 结论Los能明显改善CUMS所致的大鼠抑郁样行为，降低炎症反应、减轻氧化损伤降低，且该作用与脑内肾素-血管紧张素系统有关，为抗抑郁的靶向治疗提供了新的方向。

Anti-depressant effects of losartan on chronic unpredicted mild stress induced depression rat model

ObjectiveTo investigate effect of losartan (Los) on the behavior change of chronic unpredicted mild stress (CUMS) model rats, anti-inflammatory and antioxidant action, and explore its potential antidepressant mechanism. MethodsSprague-Dawley rats were randomly divided into 4 groups: Control group, Los group, CUMS group, and CUMS+Los group. The rats in Los group and CUMS+Los group were continuously administrated with losartan (10 mg/kg) by gavage and those in Control group and CUMS group received an equal volume of saline for 8 weeks. Sucrose preference test (SPT), forced swim test (FST) and elevated plus maze (EPM) were performed to evaluate depression-like behaviors in rats. Enzyme-linked immunosorbent assay was used to examine angiotensin Ⅱ (Ang Ⅱ) levels. RT-PCR was used to detect the mRNA expression level of Ang Ⅱ type 1 receptor (AT1R), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). The activity of superoxide dismutase (SOD) and content of malonyldialdehyde (MDA) by spectrophotometry. ResultsThere was no significant difference in consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, activity of SOD and the content of MDA between LOS group and Control group (P>0.05). Compared to the Control group, CUMS showed significantly decreased in consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, activity of SOD and significantly increased immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, the content of MDA, and the difference was statistically significant (P<0.05). The consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, activity of SOD in CUMS+Los group were higher than that in Control group, the immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, the content of MDA in CUMS+Los group were lower than that in Control group, and the difference was statistically significant (P<0.05). ConclusionLosartan can improve the depression-like behaviors of CUMS rat obviously, diminish inflammation and prevent oxygenated stress damage, which may be related to the Renin-angiotensin-system in brain and provide a new direction for the treatment of depression.