PPAR-α激动剂在OxyHb诱导的血管平滑肌细胞炎症中的作用

发布时间：2018-04-23 20:20

本文选题：蛛网膜下腔出血 + 血管痉挛　；参考：《南京中医药大学》2014年硕士论文

【摘要】：目的研究过氧化物酶体增殖物激活受体α (PPAR-α)激动剂——非诺贝特及其特异性阻断剂GW6471,对于大鼠蛛网膜下腔出血(SAH)模型脑血管痉挛的作用。方法选用100-120g SD大鼠,无菌状态下截取胸主动脉,分离血管壁中层细胞,采用贴壁法原代培养血管平滑肌细胞,传4-6代后,α-SMC-actin染色鉴定血管平滑肌细胞,选取合格细胞建立模型。将细胞分为对照组、0xyHb组(10uM OxyHb)、非诺贝特1组(OxyHb干预前1h加入100uM fenofibrate)、非诺贝特2组(OxyHb干预后0.5h加入100uM fenofibrate)、 GW1组(GW6471预先阻断非诺贝特1组)、GW2组(GW6471预先阻断非诺贝特2组),给予OxHb及相关干预因子共孵育48h后,细胞离心后收取细胞上清,采用ELISA方法检测各组细胞因子TNF-α、IL-1β的表达。结果结果提示OxyHb组TNF-α、IL-1β表达较对照组明显增加,非诺贝特1组、非诺贝特2组干预后能明显抑制细胞因子表达,而给予GW6471特异性阻断PPAR-α后细胞因子表达重新上升。提示体外SAH模型中PPAR-α激动剂非诺贝特能明显减轻血管平滑肌细胞炎症因子表达,且该作用能被GW6471特异性阻断。结论：体外SAH模型中,OxyHb组血管平滑肌细胞炎性细胞因子TNF-α、IL-1β表达较对照组明显增加,而在OxyHb诱导前或诱导后给予PPAR-α激动剂非诺贝特均能明显减轻炎症因子表达,且该作用能被PPAR-α抑制剂GW6471特异性阻断。体外验证PPAR-α激动剂非诺贝特的血管保护作用。
[Abstract]:Objective to study the effects of peroxisome proliferator activator 伪 -PPAR- 伪) agonist fenofibrate and its specific blocker GW6471 on cerebral vasospasm in rats with subarachnoid hemorrhage (SAH). Methods the aorta of 100-120 g SD rats was cut off in aseptic condition, and the vascular wall mesenchymal cells were isolated. Vascular smooth muscle cells were cultured by adherent method. After 4-6 passages, the vascular smooth muscle cells were identified by 伪 -SMC-actin staining, and qualified cells were selected to establish the model. The cells were divided into control group (10 UM OxyHb), fenofibrate 1 group (1 h before intervention), fenofibrate group 2 (0.5 h), GW1 group (GW6471) pre-blocked fenofibrate 2 group (GW6471) and fenofibrate 2 group (GW6471). OxHb and related intervention factors were incubated for 48 hours. The supernatant was collected after centrifugation and the expression of cytokine TNF- 伪 and IL-1 尾 was detected by ELISA method. The results showed that the expression of TNF- 伪-伪 IL-1 尾 in OxyHb group was significantly higher than that in control group. The expression of cytokines in fenofibrate group 1 and fenofibrate group 2 could be inhibited after intervention, but the cytokine expression increased again after GW6471 specifically blocked PPAR- 伪. It is suggested that fenofibrate, a PPAR- 伪 agonist, can significantly reduce the expression of inflammatory factors in vascular smooth muscle cells in vitro, and this effect can be blocked by GW6471. Conclusion: the expression of TNF- 伪 and IL-1 尾 in vascular smooth muscle cells in SAH group was significantly higher than that in control group, and fenofibrate, a PPAR- 伪 agonist, could significantly reduce the expression of inflammatory cytokines before and after OxyHb induction. And this effect can be specifically blocked by PPAR- 伪 inhibitor GW6471. To verify the vascular protection of PPAR- 伪 agonist fenofibrate in vitro.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.35

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