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| TLR3基因敲除通过改善线粒体生物学特性减轻肺缺血-再灌注肺损伤 |
| TLR3 gene knockout can alleviate lung ischemia-reperfusion injury by improving mitochondrial biological characteristics |
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| DOI：10.12089/jca.2020.01.016 |
| 中文关键词: Toll样受体3 线粒体转录因子A 琥珀酸脱氢酶 肺缺血-再灌注损伤 |
| 英文关键词: Toll-like receptor 3 Mitochondrial transcription factor A Succinate dehydrogenase Lung ischemia reperfusion injury |
| 基金项目:国家自然科学基金(81801962);广东省医学科学研究基金(A2018243) |
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| 中文摘要: |
目的 探讨Toll样受体3(toll-like receptor 3, TLR3)对小鼠肺缺血-再灌注(ischemia reperfusion, IR)后线粒体转录因子A(mitochondrial transcription factor A, TFAM)和琥珀酸脱氢酶(succinate dehydrogenase, SDHA)表达的影响。
方法 选取C57BL/6J野生型(WT)和TLR3基因敲除（TLR3-/-）成年小鼠各16只,体重18～22 g,随机分为四组(n=8):WT小鼠IR组(WIR组)和WT小鼠假手术组(WS组)、TLR3-/-小鼠IR组(TIR组)和TLR3-/-小鼠假手术组(TS组)。WIR组和TIR组采用夹闭左侧肺门1 h,再灌注2 h的方法制备小鼠肺IR损伤模型,WS和TS组仅开胸不夹闭左侧肺门。再灌注2 h后行动脉血气分析、检测湿干重比值、观察肺组织病理学变化;TUNEL法测定细胞凋亡并计算相应的凋亡指数;Western blot和RT-PCR方法检测肺组织中TFAM和SDHA蛋白含量和mRNA的表达水平。
结果 与WS组比较,WIR组细胞凋亡指数明显升高(P<0.05)，TFAM和SDHA蛋白含量和mRNA表达量明显降低;与WIR组比较,TIR组细胞凋亡指数明显降低（P<0.05），TFAM和SDHA蛋白含量和mRNA的表达量明显增加(P<0.05)。
结论 TLR3基因敲除可通过上调TFAM和SDHA的表达,改善线粒体功能,抑制小鼠肺IR时细胞凋亡从而减轻肺损伤。 |
| 英文摘要: |
Objective To evaluate the effect of TLR3 on the expressions of mitochondrial transcription factor A (TFAM) and succinate dehydrogenase (SDHA) during lung ischemia-reperfusion (IR) in mice.
Methods A total of 16 TLR3-/-mice and 16 WT mice, weight between 18 and 22 g, were divided into four groups (n = 8): WT mice in IR group (group WIR) and sham group (group WS),TLR3-/- mice in IR group (group TIR)and sham group (group TS). In groups WIR and TIR, the left pulmonary hilum was occluded by a noninvasive microvascular clip for 1 h, then the lung regained ventilation and reperfusion for 2 h; Mice in the groups WS and TS experienced the same procedure, but there was no process of clipping. After IR, the mice were sacrificed, arterial blood gas (ABG) levels were immediately measured, and left lungs were isolated for weigh wet/dry, examination the changes of histology, determination of cell apoptosis(by TUNEL)and TFAM and SDHA expressions (by Western blot and real-time reverse transcriptase polymerase chain reaction). The apoptosis index was calculated.
Results Compared with the group WS, the protein content and mRNA expression of TFAM and SDHA markedly decreased (P<0.05), and substantially increased the apoptosis index in group WIR (P<0.05); In addition,compared with group WIR, TLR3 deficiency significantly increased protein content and mRNA expression of TFAM and SDHA (P<0.05), and dramatically decreased the apoptosis index in group TIR (P<0.05).
Conclusion TLR3 deficiency can inhibit cell apoptosis then attenuate lung IR injury in mice, the mechanism may be related to up-regulating the expression of TFAM and SDHA. |
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