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| TGF-β/SMAD/JNK通路参与异氟醚后处理减轻大鼠局灶性脑缺血-再灌注损伤 |
| TGF-β/SMAD/JNK pathway contributes to isoflurane against cerebral ischemia-reperfusion injury |
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| DOI：10.12089/jca.2020.06.013 |
| 中文关键词: 异氟醚 后处理 脑缺血-再灌注损伤 转化生长因子-β c-Jun氨基-末端激酶 TGF-β/SMAD/JNK通路 |
| 英文关键词: Isoflurane Postconditioning Cerebral ischemia reperfusion injury Transforming growth factor beta c-Jun N terminal kinase TGF-β/SMAD/JNK pathway |
| 基金项目:国家自然科学基金（81860249， 81860209）；石河子大学科研计划项目（ZZZC201709A） |
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| 中文摘要: |
目的 探讨异氟醚后处理通过调节转化生长因子β（TGF-β）信号通路发挥脑缺血后神经保护效应，及其对下游c-Jun氨基末端激酶（JNK）的影响。
方法 雄性SD大鼠50只，体重250～300 g，随机分为五组，每组10只：假手术组（S组）、脑缺血-再灌注损伤组（IR组）、异氟醚后处理组（ISO组）、TGF-β1抑制剂组（LY组）和TGF-β1激动剂组（SR组）。S组仅做分离颈部血管的探查手术；IR组采用大脑中动脉栓塞模型(MCAO）建立脑缺血-再灌注损伤，缺血90 min，再灌注24 h；ISO组在MCAO再灌注即刻吸入1.5 %异氟醚后处理60 min；LY组和SR组分别在MCAO前30 min经脑立体定位仪侧脑室分别注射抑制剂（LY2157299）和激动剂（SRI-011381），总量为50 μl，注射10 min，注射完成后常规行MCAO和异氟醚后处理。TTC染色法及神经行为学评分判断神经损伤程度，采用TUNEL法检测神经元凋亡程度，免疫荧光染色法观察海马CA1区TGF-β1的蛋白定位，Western blot法检测海马TGF-β1及p-SMAD2/3、p-JNK1/2蛋白含量。
结果 与S组比较，IR组和ISO组神经行为学评分明显升高，神经元凋亡明显加重，TGF-β1、p-SMAD2/3和p-JNK1/2蛋白含量明显升高（P<0.05）。与IR组比较，ISO组和SR组神经行为学评分明显降低，神经元凋亡明显减轻，TGF-β1和p-SMAD2/3蛋白含量明显升高，p-JNK1/2蛋白含量明显降低（P<0.05）。与ISO组比较，LY组神经行为学评分明显升高，神经元凋亡明显加重，TGF-β1蛋白含量明显降低，p-JNK1/2蛋白含量明显升高（P<0.05）。
结论 异氟醚后处理可通过调节TGF-β1/SMAD信号通路进而抑制p-JNK1/2的表达，发挥对大鼠脑缺血-再灌注损伤的神经保护作用。 |
| 英文摘要: |
Ojective To investigate the protective effect of isoflurane postconditioning against cerebral ischemia-reperfusion (IR) injury and investigated the role of TGF-β/SMAD/JNK pathway in neuroprotective mechanism.
Methods Fifty male SD rats weighing 250-300 g, were randomly divided into five groups (10 rats in each group): sham group (group S), cerebral ischemia reperfusion injury group (group IR), isoflurane group (group ISO), LY2517299 group (group LY), SRI-011381 group (group SR). In group S, only exploration surgery was performed. In group IR, cerebral IR injury was produced by middle cerebral artery occlusion for 90 min, followed by 24 h reperfusion. Group ISO were immediately treated with 1.5% isoflurane for 60 min at the starting time of reperfusion. Rats in groups LY and SR were injected inhibitors or agonists for 30 min before middle cerebral artery occlusion model (MCAO) through the lateral ventricle of the brain stereo locator for a total of 50 μl for 10 min. MCAO and isoflurane postconditioning were routinely administered after injection. The protective effect was tested by neurological deficit scoring, TTC staining. Apoptosis cells in hippocampus was detected by TUNEL stain. The protein content were determined by immunostaining and western blot.
Results Compared with group S, the neurobehavioral scores and the neuronal apoptosis in groups IR and ISO were increased. The protein content of TGF-β1 and p-JNK1/2 were increased (P < 0.05). Compared with group IR, the neurobehavioral scores in groups ISO and SR were decreased, the neuronal apoptosis was reduced, TGF-β1 and p-SMAD2/3 were increased, p-JNK1/2 was decreased (P < 0.05). Compared with group ISO, the neurobehavioral scores in group LY were increased, neuronal apoptosis was increased, TGF-β1 was significantly decreased, p-JNK1/2 was increased (P < 0.05).
Conclusion Isoflurane postconditioning can upregulate the expression of TGF-β1 and downregulate p-JNK, which acts against cerebral IR injury. |
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