BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs37...BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs372369000 is a risk locus for MDD and is located within the B4GALT6 gene.However,the biological and pathological implications of B4GALT6 in the brain concerning MDD remain unclear.AIM To reveal the biological and pathological significance of B4GALT6 in the brain and MDD.METHODS An inflammation-associated depression mouse model was developed by treating mice with lipopolysaccharides.B4GALT6-like immunoreactivity distribution and expression level was examined throughout the brain.RESULTS B4GALT6-like immunoreactivity increased in the hippocampus,PrL,and the visual cortex V1 region of MDD mice.This elevation varied across different brain subregions and cell types.Specifically,pathological alterations in B4GALT6-like immunoreactivity were observed in CA1 microglia,CA2 neurons,CA3 microglia and neurons,as well as V1 microglia and astrocytes.These changes correlated with the pathology of depression.CONCLUSION Although the neuropathological role of B4GALT6 in the brain remains to be fully characterized,B4GALT6 may be a potential therapeutic target for MDD.展开更多
目的:基于核心1β1,3-半乳糖基转移酶(C1GALT1)及其伴侣蛋白Cosmc(C1GALT1/Cosmc通路)研究雷公藤多苷(TWM)对IgA肾病(IgAN)大鼠肠道菌群及免疫功能的影响。方法:构建IgAN大鼠模型,随机分为模型组(IgAN组)、地塞米松(Dex)组和TWM组,另设...目的:基于核心1β1,3-半乳糖基转移酶(C1GALT1)及其伴侣蛋白Cosmc(C1GALT1/Cosmc通路)研究雷公藤多苷(TWM)对IgA肾病(IgAN)大鼠肠道菌群及免疫功能的影响。方法:构建IgAN大鼠模型,随机分为模型组(IgAN组)、地塞米松(Dex)组和TWM组,另设正常饲养大鼠为正常对照(NC)组。采用全自动生化分析仪测定各组大鼠血清肌酐(SCr)、血尿素氮(BUN)、24 h尿总蛋白量(UTP)及24 h尿红细胞数;ELISA法检测各组大鼠血清IgA1水平及血浆肿瘤坏死因子α(TNF-α)、B细胞活化因子(Baff)和白细胞介素17(IL-17)水平;蚕豆凝集素亲和ELISA法检测半乳糖缺乏IgA1(Gd-IgA1)水平;选择性细菌培养基培养肠道菌落;流式细胞术检测外周血单个核细胞(PBMC)中CD4+CD25+调节性T细胞(Treg)占CD4+T细胞比例(简称Treg比例);Western blot法检测肠黏膜组织C1GALT1和Cosmc的蛋白表达。结果:与NC组比较,IgAN组大鼠24 h UTP和尿红细胞数,SCr和BUN水平,血清IgA1和Gd-IgA1水平,肠道肠杆菌、肠球菌和拟杆菌数量,以及血浆TNF-α、Baff和IL-17水平均显著增加(P<0.05),而双歧杆菌和乳酸杆菌数量、PBMC中Treg比例及肠黏膜组织中C1GALT1和Cosmc蛋白表达水平显著降低(P<0.05);与IgAN组比较,Dex组和TWM组大鼠24 h UTP和尿红细胞数,SCr和BUN水平,血清IgA1和Gd-IgA1水平,肠道肠杆菌、肠球菌和拟杆菌数量,以及血浆TNF-α、Baff和IL-17水平均显著降低(P<0.05),且TWM组低于Dex组(P<0.05),双歧杆菌和乳酸杆菌数量、PBMC中Treg比例及肠黏膜组织中C1GALT1和Cosmc蛋白表达水平显著增加(P<0.05),且TWM组高于Dex组(P<0.05)。结论:TWM可通过促进C1GALT1/Cosmc通路激活降低IgAN大鼠IgA异常糖基化水平,并减轻IgAN大鼠肠道菌群紊乱及免疫功能失调,从而发挥治疗效果。展开更多
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2025JJ80473 and No.2025JJ80484the Institute of Hospital Management,National Health Commission of China,Major Project,No.SZ2024HL021.
文摘BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs372369000 is a risk locus for MDD and is located within the B4GALT6 gene.However,the biological and pathological implications of B4GALT6 in the brain concerning MDD remain unclear.AIM To reveal the biological and pathological significance of B4GALT6 in the brain and MDD.METHODS An inflammation-associated depression mouse model was developed by treating mice with lipopolysaccharides.B4GALT6-like immunoreactivity distribution and expression level was examined throughout the brain.RESULTS B4GALT6-like immunoreactivity increased in the hippocampus,PrL,and the visual cortex V1 region of MDD mice.This elevation varied across different brain subregions and cell types.Specifically,pathological alterations in B4GALT6-like immunoreactivity were observed in CA1 microglia,CA2 neurons,CA3 microglia and neurons,as well as V1 microglia and astrocytes.These changes correlated with the pathology of depression.CONCLUSION Although the neuropathological role of B4GALT6 in the brain remains to be fully characterized,B4GALT6 may be a potential therapeutic target for MDD.
文摘目的:基于核心1β1,3-半乳糖基转移酶(C1GALT1)及其伴侣蛋白Cosmc(C1GALT1/Cosmc通路)研究雷公藤多苷(TWM)对IgA肾病(IgAN)大鼠肠道菌群及免疫功能的影响。方法:构建IgAN大鼠模型,随机分为模型组(IgAN组)、地塞米松(Dex)组和TWM组,另设正常饲养大鼠为正常对照(NC)组。采用全自动生化分析仪测定各组大鼠血清肌酐(SCr)、血尿素氮(BUN)、24 h尿总蛋白量(UTP)及24 h尿红细胞数;ELISA法检测各组大鼠血清IgA1水平及血浆肿瘤坏死因子α(TNF-α)、B细胞活化因子(Baff)和白细胞介素17(IL-17)水平;蚕豆凝集素亲和ELISA法检测半乳糖缺乏IgA1(Gd-IgA1)水平;选择性细菌培养基培养肠道菌落;流式细胞术检测外周血单个核细胞(PBMC)中CD4+CD25+调节性T细胞(Treg)占CD4+T细胞比例(简称Treg比例);Western blot法检测肠黏膜组织C1GALT1和Cosmc的蛋白表达。结果:与NC组比较,IgAN组大鼠24 h UTP和尿红细胞数,SCr和BUN水平,血清IgA1和Gd-IgA1水平,肠道肠杆菌、肠球菌和拟杆菌数量,以及血浆TNF-α、Baff和IL-17水平均显著增加(P<0.05),而双歧杆菌和乳酸杆菌数量、PBMC中Treg比例及肠黏膜组织中C1GALT1和Cosmc蛋白表达水平显著降低(P<0.05);与IgAN组比较,Dex组和TWM组大鼠24 h UTP和尿红细胞数,SCr和BUN水平,血清IgA1和Gd-IgA1水平,肠道肠杆菌、肠球菌和拟杆菌数量,以及血浆TNF-α、Baff和IL-17水平均显著降低(P<0.05),且TWM组低于Dex组(P<0.05),双歧杆菌和乳酸杆菌数量、PBMC中Treg比例及肠黏膜组织中C1GALT1和Cosmc蛋白表达水平显著增加(P<0.05),且TWM组高于Dex组(P<0.05)。结论:TWM可通过促进C1GALT1/Cosmc通路激活降低IgAN大鼠IgA异常糖基化水平,并减轻IgAN大鼠肠道菌群紊乱及免疫功能失调,从而发挥治疗效果。
