牛磺酸对抑郁症大鼠的保护作用及机制研究

Protective effect and mechanism of taurine on depression rats

目的探讨牛磺酸对抑郁症大鼠海马神经细胞的影响,以及核因子E2相关因子2(Nrf2)/血红素氧化酶-1(HO-1)/醌氧化还原酶1(NQO1)信号通路所发挥的作用。方法将60只8周龄SD雄性大鼠随机分成对照组、慢性轻度不可预测的刺激(CUMS)模型组(简称CUMS模型组)、牛磺酸低剂量组、牛磺酸高剂量组和氟西汀组,每组12只。采用CUMS法制备抑郁症大鼠模型。牛磺酸低、高剂量组大鼠分别给予200、500 mg/kg牛磺酸腹腔注射,氟西汀组给予10 mg/kg氟西汀灌胃干预,对照组和CUMS模型组给予等量生理盐水灌胃,共7 d。采用蔗糖偏好实验和强迫游泳实验检测各组大鼠行为学;检测各组大鼠血清促肾上腺皮质激素(ACTH)和皮质酮(CORT)水平;检测各组海马组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)水平;Western blot检测海马组织中Nrf2、HO-1、NQO1蛋白表达水平。结果与对照组比较,CUMS模型组大鼠游泳不动时间、血清ACTH和CORT水平、海马组织MDA水平、神经元凋亡率显著升高(均P<0.05),蔗糖偏好、SOD、GSH-Px水平及Nrf2、HO-1、NQO1蛋白表达水平降低(P<0.05)。与CUMS模型组比较,牛磺酸低、高剂量组和氟西汀组游泳不动时间、血清ACTH和CORT水平、海马组织MDA水平、神经元凋亡率显著降低(均P<0.05),蔗糖偏好、SOD、GSH-Px水平及Nrf2、HO-1、NQO1蛋白表达水平显著升高(均P<0.05);氟西汀组和牛磺酸高剂量组间上述指标比较差异无统计学意义(P>0.05)。结论牛磺酸对抑郁症大鼠具有抗抑郁作用,其机制可能与牛磺酸激活Nrf2/HO-1/NQO1通路进而抑制氧化应激反应有关。

Objective To investigate the effect of taurine on hippocampal nerve cells in depression rats,and the role of nuclear factor E2-related factor 2(Nrf2)/heme oxidase-1(HO-1)/quinone oxidoreductase 1(NQO1)signaling pathway.Methods Sixty male SD rats aged 8 weeks were randomly divided into a normal group,a chronic mild unpredictable stimulation(CUMS)model group(CUMS model group),a taurine low-dose group,a taurine high-dose group,and a fluoxetine group,with 12 rats in each group.The depression rat model was established by the CUMS method.The low-dose and high-dose taurine groups were intraperitoneally injected with 200 and 500 mg/kg taurine,the fluoxetine group was given 10 mg/kg fluoxetine,the normal group and CUMS group were given the same amount of normal saline,for a total of 7 days.Sucrose preference test and forced swimming test were used to test the behavior of rats in each group.Serum adrenocorticotropic hormone(ACTH)and corticosterone(CORT)levels were detected.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in the hippocampus were detected.The expression levels of Nrf2,HO-1 and NQO1 proteins in the hippocampus were detected by Western blot.Results Compared with the normal group,the swimming immobility time,serum ACTH and CORT levels,hippocampal MDA levels,and neuronal apoptosis rate of rats in the CUMS group were significantly increased(P<0.05),the sucrose preference,SOD and GSH-Px levels and Nrf2,HO-1,and NQO1 protein expression levels were reduced(all P<0.05).Compared with the CUMS group,the swimming immobility time,serum ACTH and CORT levels,hippocampal MDA levels,and neuronal apoptosis rate of rats in the taurine low-dose and high-dose groups and the fluoxetine group were significantly reduced(all P<0.05),the sucrose preference,SOD and GSH-Px levels and Nrf2,HO-1,and NQO1 protein expression levels were significantly increased(all P<0.05).There was no significant difference in the above indices between the fluoxetine group and the taurine high-dose group(P>0.05).Conclusions Taurine has an antidepressant effect on depressed rats,and the mechanism may be related to the activation of Nrf2/HO-1/NQO1 pathway by taurine to inhibit oxidative stress response.