瞬时感受器电位香草素受体亚家族Ⅳ型抑制剂HC067047对脂多糖诱导的小鼠焦虑样行为的影响

doi:10.16098/j.issn.0529-1356.2023.02.004

摘要/Abstract

摘要：

目的探讨瞬时感受器电位香草素受体亚家族Ⅳ型（TRPV4）抑制剂HC067047对脂多糖(LPS)模型小鼠焦虑样行为的影响。方法 48只雄性C57BL/6小鼠随机分为对照组（NS）、模型组（LPS）和药物干预组（HC+LPS）。腹腔注射0.83 mg/kg LPS建立焦虑样小鼠模型，HC+LPS组于LPS注射前30 min腹腔注射HC067047（10 mg/kg）， NS组及LPS组注射等体积溶媒；旷场实验以及社会交往实验观察小鼠焦虑样行为；免疫组织化学及Western blotting检测海马TRPV4、诱导型一氧化氮合酶（iNOS）、神经型一氧化氮合酶(nNOS) 和内皮型一氧化氮合酶(eNOS) 的表达情况。结果免疫组织化学和Western blotting实验发现，与NS组相比，LPS组小鼠海马中TRPV4表达显著上调（P＜0.0001）；旷场实验中，与NS组比较，发现LPS组小鼠活动的总距离（P＜0.0001）、在中央区域活动的距离（P＜0.01）以及在中央区域活动的时间均明显减少（P＜0.01），HC067047干预可增加LPS模型小鼠的活动总距离（P＜0.05）、在中央区域活动的距离（P＜0.001）以及在中央区域的活动时间（P＜0.01）；社会交往实验中，与NS组相比，LPS组小鼠与陌生小鼠的交往时间显著降低（P＜0.01），HC067047干预后能显著增加LPS模型小鼠与陌生小鼠的交往时间（P＜0.01）；Western blotting检测发现，LPS组小鼠海马中iNOS（P＜0.05）、nNOS（P＜0.001）和eNOS（P＜0.001）的表达显著高于NS组，但HC067047干预后可使LPS模型小鼠海马中iNOS（P＜0.05）、nNOS（P＜0.01）、eNOS（P＜0.01）的表达明显降低。结论抑制TRPV4的表达能够改善LPS所致小鼠焦虑样行为，该过程可能与抗氧化应激有关。

关键词: 瞬时感受器电位香草素受体亚家族Ⅳ型, HC067047, 焦虑症, 氧化应激, 一氧化氮合酶, 免疫印迹法, 小鼠

Abstract:

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4）inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC+LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC+LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P＜0.0001); In the open field test, compared with the NS group, the total distance (P<0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P<0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P＜0.05), the distance of activities in the central area (P＜0.001) and the time of in the central area (P＜0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P＜0.05), nNOS (P＜0.001), and eNOS (P＜0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P<0.05, nNOS P<0.01 and eNOS P<0.01). Conclusionn Inhibiting the expression of TRPV4 can improve the anxietylike behavior, and this process may be related to anti-oxidative stress.

Key words: Transient receptor potential vanilloid 4, HC067047, Anxiety disorder, Oxidative stress, Nitric oxide synthase, Western blotting, Mouse

中图分类号:

R322.81

郭东铭张静文黄新磊徐杨熊天庆曹文宇梁景岩 . 瞬时感受器电位香草素受体亚家族Ⅳ型抑制剂HC067047对脂多糖诱导的小鼠焦虑样行为的影响[J]. 解剖学报, 2023, 54(2): 149-155.

GUO Dong-ming ZHANG Jing-wen HUANG Xin-lei XU Yang XIONG Tian-qing CAO Wen-yu LIANG Jing-yan . Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide[J]. Acta Anatomica Sinica, 2023, 54(2): 149-155.

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