摘要
目的:探讨核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路在迷迭香酸(RA)保护抑郁模型大鼠中的作用。方法:采用孤养结合慢性不可预知性轻度应激(CUMS)法复制抑郁症大鼠模型,将60只SPF级6周龄雄性SD大鼠随机分为对照(Cont)组、CUMS组、CUMS+RA(10 mg/kg)组和CUMS+RA(10 mg/kg)+Nrf2抑制剂(Nrf2-IN-1,1 mg/kg)组(n=15)。CUMS造模3周后开始给药,连续3周。采用糖水偏好实验、强迫游泳实验和悬尾实验观察大鼠的抑郁样行为,采用HE染色和免疫荧光实验观察海马神经元损伤和小胶质细胞浸润情况,Western blot检测Nrf2/HO-1信号通路相关蛋白的表达,试剂盒检测活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、白细胞介素6(IL-6)、IL-1β和肿瘤坏死因子α(TNF-α)的水平。结果:与Cont组相比,CUMS组表现出神经元排列疏松紊乱、胞核皱缩、小胶质细胞活化等损伤,强迫游泳和悬尾静止时间延长(P<0.05),IL-6、IL-1β、TNF-α、ROS和MDA水平升高(P<0.05),糖水偏爱指数、SOD活性及HO-1、NAD(P)H:醌氧化还原酶1(NQO1)、脑源性神经营养因子(BDNF)和核/质Nrf2蛋白表达降低(P<0.05)。RA治疗可明显减轻上述损伤,缩短强迫游泳和悬尾静止时间(P<0.05),降低IL-6、IL-1β、TNF-α、ROS和MDA水平(P<0.05),上调糖水偏爱指数、SOD活性及HO-1、NQO1、BDNF和核/质Nrf2蛋白表达(P<0.05)。与CUMS+RA组相比,CUMS+RA+Nrf2-IN-1组上述指标均显著逆转(P<0.05)。结论:RA可通过活化Nrf2/HO-1通路,减轻海马组织氧化应激和炎症损伤,减少CUMS所致大鼠抑郁样行为。
AIM:To investigate the role of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in the protective effect of rosmarinic acid(RA)on depressive rats.METHODS:Individual rearing combined with chronic unpredictable mild stress(CUMS)was used to replicate the depression rat model.A total of 60 SD rats were randomly divided into 4 groups(n=15):control group,CUMS group,CUMS+RA(10 mg/kg)group and CUMS+RA(10 mg/kg)+Nrf2 inhibitor(Nrf2-IN-1,1 mg/kg)group.The administration started after 3 weeks of CUMS for 3 con-secutive weeks.The sugar water preference test,forced swimming test and tail suspension test were used to observe the de-pression-like behaviors.HE staining and immunofluorescence staining were used to observe hippocampal neuron damage and microglia infiltration.Western blot was used to detect the Nrf2/HO-1 signaling pathway-related protein expression,and the levels of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),interleukin-6(IL-6),IL-1βand tumor necrosis factor-α(TNF-α)were also measured.RESULTS:Compared with control group,CUMS group showed loose and disordered neuron arrangement,shrinkage of the nucleus,and activation of microglia,the forced swimming rest time and tail suspension rest time were prolonged(P<0.05),the levels of IL-6,IL-1β,TNF-α,ROS and MDA were increased(P<0.05),and the sugar preference index,SOD activity,and HO-1,NAD(P)H:quinone oxidoreductase 1(NQO1),brain-derived neurotrophic factor(BDNF)and nuclear/cytoplasmic Nrf2 protein expression were decreased(P<0.05).Treatment with RA significantly attenuated the above-mentioned injuries,shortened the forced swimming rest time and tail suspension rest time(P<0.05),reduced the levels of IL-6,IL-1β,TNF-α,ROS and MDA(P<0.05),and increased the sugar preference index,SOD activity,and HO-1,NQO1,BDNF and nuclear/cytoplasmic Nrf2 protein expression(P<0.05).Compared with CUMS+RA group,the above indicators in CUMS+RA+Nrf2-IN-1 group were significantly reversed(P<0.05).CONCLUSION:Treatment with RA a
作者
赖根祥
朱桂东
何慧明
LAI Gen-xiang;ZHU Gui-dong;HE Hui-ming(Department of Psychiatry,Lishui Second People's Hospital,Faculty of Medicine and Health,Lishui University,Lishui 323000,China;Scientific Research Office,Faculty of Medicine and Health,Lishui University,Lishui 323000,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2021年第7期1195-1201,共7页
Chinese Journal of Pathophysiology
基金
丽水市科技计划项目(No.2019SJZC17)。
