淫羊藿苷对抑郁症模型小胶质细胞表型转化的调控作用
R964; 探索淫羊藿苷抗抑郁的作用机制,将SPF级KM小鼠分为空白组、模型组、盐酸氟西汀组(10 mg/kg)、淫羊藿苷高(50 mg/kg)、低(25 mg/kg)剂量组.除空白组外,其余各组小鼠采用56 d慢性不可预知温和应激建立抑郁症模型.造模第1 d开始灌胃给予各组小鼠相应药物,连续56 d.于给药后第53～56d,进行行为学测试.末次给药后,取材.酶联免疫吸附剂实验(enzyme linked immunosorbent assay,ELISA)检测脑组织匀浆白细胞介素6(interleukin-6,IL-6)、白细胞介素 10(interleukin-10,IL-10)、五羟色胺...
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| Published in | 天然产物研究与开发 Vol. 36; no. 2; pp. 187 - 195 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
河南中医药大学中医药科学院,郑州 450046
23.02.2024
仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%河南中医药大学中医药科学院,郑州 450046%河南中医药大学药学院,郑州 450046 |
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| Online Access | Get full text |
| ISSN | 1001-6880 |
| DOI | 10.16333/j.1001-6880.2024.2.001 |
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| Abstract | R964; 探索淫羊藿苷抗抑郁的作用机制,将SPF级KM小鼠分为空白组、模型组、盐酸氟西汀组(10 mg/kg)、淫羊藿苷高(50 mg/kg)、低(25 mg/kg)剂量组.除空白组外,其余各组小鼠采用56 d慢性不可预知温和应激建立抑郁症模型.造模第1 d开始灌胃给予各组小鼠相应药物,连续56 d.于给药后第53～56d,进行行为学测试.末次给药后,取材.酶联免疫吸附剂实验(enzyme linked immunosorbent assay,ELISA)检测脑组织匀浆白细胞介素6(interleukin-6,IL-6)、白细胞介素 10(interleukin-10,IL-10)、五羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)水平;实时荧光定量 PCR(quantitative real-time PCR,RT-PCR)检测脑组织中 IL-6、IL-10、诱导性一氧化氮合酶(inducible nitric oxide synthase,iNOS)、分化簇 206(cluster of differentiation 206,CD206)mRNA 表达;蛋白免疫印迹(Western blot)检测脑组织iNOS、CD206蛋白表达.体外培养小鼠小胶质细胞(BV-2),采用细胞增殖与毒性检测试剂盒(Cell Counting Kit-8,CCK-8)法检测淫羊藿苷的细胞毒性.BV-2细胞暴露于100μg/mL脂多糖及15 μg/mL、25 μg/mL的淫羊藿苷24 h后,收集细胞.免疫荧光技术检测细胞iNOS、CD206蛋白表达.研究结果表明,慢性不可预知温和应激致抑郁症模型制备成功,淫羊藿苷可降低抑郁症小鼠脑组织IL-6水平及IL-6、iNOS mRNA表达,升高脑组织IL-10、5-HT、DA、NE水平及IL-10、CD206 mRNA表达;降低脑组织iNOS蛋白,升高CD206蛋白表达;改善模型小鼠抑郁症样行为.淫羊藿苷可降低LPS刺激的BV-2细胞iNOS蛋白表达,升高CD206蛋白表达.结果表明,淫羊藿苷抑制小胶质细胞M1表型转化,促进M2表型转化,从而改善模型小鼠抑郁样行为. |
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| AbstractList | R964; 探索淫羊藿苷抗抑郁的作用机制,将SPF级KM小鼠分为空白组、模型组、盐酸氟西汀组(10 mg/kg)、淫羊藿苷高(50 mg/kg)、低(25 mg/kg)剂量组.除空白组外,其余各组小鼠采用56 d慢性不可预知温和应激建立抑郁症模型.造模第1 d开始灌胃给予各组小鼠相应药物,连续56 d.于给药后第53～56d,进行行为学测试.末次给药后,取材.酶联免疫吸附剂实验(enzyme linked immunosorbent assay,ELISA)检测脑组织匀浆白细胞介素6(interleukin-6,IL-6)、白细胞介素 10(interleukin-10,IL-10)、五羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)水平;实时荧光定量 PCR(quantitative real-time PCR,RT-PCR)检测脑组织中 IL-6、IL-10、诱导性一氧化氮合酶(inducible nitric oxide synthase,iNOS)、分化簇 206(cluster of differentiation 206,CD206)mRNA 表达;蛋白免疫印迹(Western blot)检测脑组织iNOS、CD206蛋白表达.体外培养小鼠小胶质细胞(BV-2),采用细胞增殖与毒性检测试剂盒(Cell Counting Kit-8,CCK-8)法检测淫羊藿苷的细胞毒性.BV-2细胞暴露于100μg/mL脂多糖及15 μg/mL、25 μg/mL的淫羊藿苷24 h后,收集细胞.免疫荧光技术检测细胞iNOS、CD206蛋白表达.研究结果表明,慢性不可预知温和应激致抑郁症模型制备成功,淫羊藿苷可降低抑郁症小鼠脑组织IL-6水平及IL-6、iNOS mRNA表达,升高脑组织IL-10、5-HT、DA、NE水平及IL-10、CD206 mRNA表达;降低脑组织iNOS蛋白,升高CD206蛋白表达;改善模型小鼠抑郁症样行为.淫羊藿苷可降低LPS刺激的BV-2细胞iNOS蛋白表达,升高CD206蛋白表达.结果表明,淫羊藿苷抑制小胶质细胞M1表型转化,促进M2表型转化,从而改善模型小鼠抑郁样行为. |
| Abstract_FL | This study aims to explore the antidepressant mechanism of icariin.Mice(SPF,KM)were randomly divided into five groups,including the control group,model group,fluoxetine hydrochloride group,high-dose icariin group,and low-dose icariin group.Mice were subjected to different stressors for 56 days except control group mice.Meanwhile,groups of mice were intragastrically administered fluoxetine hydrochloride(10 mg/kg),high-dose icariin(50 mg/kg),low-dose icariin(25 mg/kg)or a vehicle once per day for 56 consecutive days.On the 53 th-56 th day after administration,behavioral tests were per-formed.At the end of the treatment,blood was collected using cardiac puncture under anesthesia.ELISA was used to detect interleukin-6(IL-6),IL-10,5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)level.The expression of IL-6,IL-10,inducible nitric oxide synthase(iNOS)and cluster of differentiation 206(CD206)mRNA in brain tissue were detected using quantitative real-time PCR(RT-PCR).Western blot was used to detect the expression of iNOS and CD206 protein in brain tissue.BV-2 cells were cultured in vitro,and CCK-8 method was used to detect the cytotoxicity of icariin.Af-ter the exposure of BV-2 cells to lipopolysaccharide(LPS)(100 μg/mL)and icariin(15,25 μg/mL)for 24 h.The expres-sion of iNOS and CD206 mRNA in brain tissue were detected using immunofluorescence.We found that the model of depres-sion caused by chronic unpredictable mild stress was successful.Icariin reduced the level of IL-6 and the expression of IL-6,iNOS mRNA in the brain tissue of depression mice,increased the level of IL-10,5-HT,DA,NE and the expression of IL-10,CD206 mRNA,inhibited the brain iNOS protein and increase the expression of CD206 protein,and improved depression-like behavior in model mice.The results of in vitro studies show that icariin could reduce the expression of iNOS and protein in BV-2 cells stimulated by LPS,and increased the expression of CD206 and protein.The results show that icariin inhibits the M1 phenotype transformation of microglia and promotes the M2 phenotype transformation,thereby improving the depression-like behavior of model mice. |
| Author | 曹利华 李娜 王笑雨 高松 苗明三 贺红娟 王真真 白明 |
| AuthorAffiliation | 河南中医药大学中医药科学院,郑州 450046;仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%河南中医药大学中医药科学院,郑州 450046%河南中医药大学药学院,郑州 450046 |
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| Author_FL | BAI Ming GAO Song WANG Xiao-yu HE Hong-juan LI Na WANG Zhen-zhen MIAO Ming-san CAO Li-hua |
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| Keywords | 小胶质细胞表型转化 淫羊藿苷 细胞炎症模型 抑郁症 icariin microglia phenotypic transformation depression cellular inflammation model |
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| Publisher | 河南中医药大学中医药科学院,郑州 450046 仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,西峡 474550%河南中医药大学中医药科学院,郑州 450046%河南中医药大学药学院,郑州 450046 |
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| Title | 淫羊藿苷对抑郁症模型小胶质细胞表型转化的调控作用 |
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