机构地区:[1]宜昌市优抚医院精神科,湖北宜昌443005 [2]三峡大学第二人民医院心理科,湖北宜昌443005 [3]宜昌市中心人民医院感染科,湖北宜昌443005 [4]武汉科技大学附属医院精神科,湖北武汉430000
出 处:《局解手术学杂志》2021年第5期379-384,共6页Journal of Regional Anatomy and Operative Surgery
基 金:湖北省自然科学基金(2018CFB476)。
摘 要:目的探讨肿瘤坏死因子受体相关因子6(TRAF6)对慢性不可预知性轻度应激(CUMS)大鼠的抗抑郁作用。方法将40只健康SPF级SD大鼠随机分为对照组、模型组(CUMS组)、CUMS+shRNA-NC组和CUMS+TRAF6-shRNA组,每组10只。除对照组外,所有大鼠每天随机接受CUMS刺激,5周后,分别向CUMS+shRNA-NC组和CUMS+TRAF6-shRNA组大鼠海马区注射慢病毒包被的shRNA-NC和TRAF6-shRNA序列。RT-PCR和Western blot检测TRAF6 mRNA和蛋白的表达;ELISA检测大鼠血清中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、TNF-α、iNOS、IL-6和IL-10的含量;酶法测定大鼠血清血脂;HE染色观察海马区病理状况;TUNEL染色检测海马区细胞凋亡情况;Western blot检测海马谷氨酸转运体(GLT-1)和脑源性神经营养因子(BDNF)及凋亡蛋白的表达。结果与对照组相比,CUMS组大鼠海马区TRAF6 mRNA和蛋白表达量明显上调(P<0.05),GLT-1和BDNF蛋白表达显著下调(P<0.05),血清中5-HT和5-HIAA水平显著较低(P<0.05),TC、TG和LDL-c水平较高(P<0.05),HDL-c水平较低(P<0.05);大鼠血脂代谢紊乱,海马区神经元数量减少,核固缩;凋亡细胞数目明显较多(P<0.05),Bax/Bcl-2及cleaved Caspase3/Caspase3比值显著上调(P<0.05);TNF-α、iNOS、IL-6和IL-10含量明显较高(P<0.05)。与CUMS组相比,CUMS+TRAF6-shRNA组大鼠海马区TRAF6 mRNA和蛋白表达量明显下调(P<0.05),GLT-1和BDNF蛋白表达显著上调,血清5-HT和5-HIAA水平较高(P<0.05),TC、TG和LDL-c水平较低(P<0.05),HDL-c水平较高(P<0.05);海马区神经元完整,很少有核固缩;凋亡细胞数目明显较少(P<0.05),Bax/Bcl-2及cleaved Caspase3/Caspase3比值显著下调(P<0.05),TNF-α、iNOS、IL-6含量显著较低(P<0.05),IL-10含量较高(P<0.05)。结论敲低TRAF6水平治疗抑郁症大鼠可能是通过调节大鼠神经递质、抑制海马神经元凋亡并抑制炎症反应来实现。Objective To explore the antidepressant effect of tumor necrosis factor receptor-associated factor 6(TRAF6)on chronic unpredictable mild stress(CUMS)rats.Methods Forty healthy SPF Sprague-Dawley(SD)rats were randomly divided into the control group,the model group(CUMS group),the CUMS+shRNA-NC group and the CUMS+TRAF6-shRNA group,with 10 rats in each group.Except for the control group,all rats were randomly stimulated by CUMS every day.After 5 weeks,the CUMS+shRNA-NC group and the CUMS+TRAF6-shRNA group were respectively injected with lentiviral-coated shRNA-NC and TRAF6-shRNA sequences into the hippocampus of rats.RT-PCR and Western blot were used to detect the expression of TRAF6 mRNA and protein.ELISA was used to assay the content of 5-hydroxytryptamine(5-HT),5-hydroxyindoleacetic acid(5-HIAA),TNF-α,iNOS,IL-6 and IL-10 in rat serum.Serum lipids of rats were determined by enzymatic method.HE staining was performed to observe the pathological status of hippocampus.TUNEL staining was commended to determine cell apoptosis of hippocampus.Western blot was employed to measure the expression of hippocampal glutamate transporter 1(GLT-1),brain-derived neurotrophic factor(BDNF),and apoptosis proteins.Results Compared with the control group,the expression levels of TRAF6 mRNA and protein were significantly up-regulated(P<0.05);the expression of GLT-1 and BDNF protein were significantly down-regulated(P<0.05);the levels of 5-HT and 5-HIAA in rat sreum were significantly lower(P<0.05);the levels of TC,TG and LDL-c were significantly higher(P<0.05);the level of HDL-c was significantly lower in the CUMS group(P<0.05).In the CUMS group,rat blood lipid metabolism was disordered,the number of neurons in the hippocampus was reduced,and the nucleus was constricted;the number of apoptotic cells increased significantly(P<0.05);the ratio of Bax/Bcl-2 and cleaved Caspase3/Caspase3 were significantly up-regulated(P<0.05);the levels of TNF-α,iNOS,IL-6 and IL-10 were significantly higher(P<0.05).Compared with the CUMS group,the express
关 键 词:抑郁症 TRAF6 慢性不可预知性轻度应激 BDNF 凋亡 炎症
分 类 号:R749.4[医药卫生—神经病学与精神病学]
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