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抗抑郁药对TNF-α 诱导的神经细胞凋亡的作用 机制
陆晓星方刚张海冬
0
()
摘要:
目的 探讨抗抑郁药对TNF-α诱导的神经细胞存活和凋亡的影响及机制。方法 将小 鼠海马神经元细胞HT22 分为5 组:对照组、TNF-α组、米安色林组、米氮平组和阿米替林组。后3 组先 用对应的抗抑郁药处理30 min,然后除对照组外,其余4 组均用TNF-α 处理24 h。MTT 法检测各组细 胞存活率,Annexin V-FITC/PI 双染法检测细胞凋亡率,Western Blot 检测相关蛋白的表达。结果 抗抑 郁药可增加TNF-α 诱导的神经细胞的存活率,降低TNF-α 诱导的细胞凋亡率,降低TNF-α 诱导的细 胞色素C 的释放及Caspase-9、Caspase-3 和Cleaved PARP 的活性,对Caspase-8 的活性无显著影响。抗抑 郁药对肿瘤坏死因子受体(TNFR)1 和TNFR2 的表达以及IKBα 和NF-κB p65 的活性无显著影响。抗 抑郁药可增加TNF-α 诱导的溶血磷脂酸1(LPA1)和成纤维细胞生长因子受体(FGFR)表达以及JNK 和 ERK1/2 的活性。结论 抗抑郁药可促进TNF-α 诱导的神经细胞的存活,降低TNF-α 诱导的神经细胞 凋亡,促进TNF-α 诱导LPA1/FGFR通路的表达,激活TNF-α 诱导JNK通路和ERK1/2 通路。
关键词:  抗抑郁药  细胞存活  细胞凋亡  LPA1/FGFR  JNK  ERK1/2
DOI:10.3969/j.issn.1009-6574.2019.06.010
基金项目:
Mechanisms of antidepressants inhibiting TNF-α-induced neuronal apoptosis
Lu Xiaoxing, Fang Gang, Zhang Haidong
()
Abstract:
Objective To investigate the effects and mechanisms of antidepressants on TNF-α- induced neuronal survival and apoptosis. Methods Mouse hippocampal neuronal cells HT22 were divided into 5 groups: control group, TNF-α group, mianserin group, mirtazapine group and amitriptyline group. The last three groups were first treated with the assigned antidepressant for 30 min. All groups except the control group were then treated with TNF-α for 24 h. The neuronal survival rate of each group was detected by the MTT method. The neuronal apoptosis rate was detected by the Annexin V-FITC/PI double staining method. Expressions of related proteins were detected by the Western Blot. Results Antidepressants increased TNF- α-induced neuronal survival rate, reduced TNF-α-induced cell apoptosis rate, TNF-α-induced cytochrome c release, activities of caspase-9, caspase-3, and Cleaved PARP. However, antidepressants had no significant effect on the activity of caspase-8 in any group. Antidepressants also had no significant effect on the expressions of TNFR1 and TNFR2 or the activity of IKBα and NF-κB p65. Antidepressants increased TNF-α-induced LPA1 and FGFR expression as well as JNK and ERK1/2 activity. Conclusions Antidepressants can promote TNF-α-induced neuronal survival, reduce TNF-α-induced neuronal apoptosis, enhancing the TNF-α- induced expression of LPA1/FGFR pathway and activating JNK and ERK1/2 pathways.
Key words:  Antidepressants  Cell survival  Apoptosis  LPA1/FGFR  JNK  ERK1/2

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