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| 激活PPAR-γ对脑缺血-再灌注损伤中炎症反应的影响 |
| Effects of PPAR-γ activation on inflammation in cerebral ischemia and reperfusion injury |
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| DOI：10.12089/jca.2020.07.013 |
| 中文关键词: 过氧化物酶体增殖物激活受体-γ；脑缺血-再灌注损伤；细胞焦亡 半胱天冬酶-1 |
| 英文关键词: Peroxisome proliferator-activated receptor-γ Cerebral ischemia-reperfusion injury Pyroptosis Caspase-1 |
| 基金项目:国家自然科学基金（81771422）；湖南省自然科学基金（2019JJ50969） |
| 作者 | 单位 | E-mail | | 黄炎 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 彭拓 | 武汉大学中南医院麻醉科 | | | 陈诚 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 夏萍萍 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 张帆 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 李龙艳 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 叶治 | 410000,长沙市,中南大学湘雅医院麻醉科 | | | 贺正华 | 410000,长沙市,中南大学湘雅医院麻醉科 | xymz99@163.com |
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| 中文摘要: |
目的 探究激活过氧化物酶体增殖物激活受体-γ（PPAR-γ）对脑缺血-再灌注损伤（CIRI）与脂多糖（LPS）诱导炎症反应的影响。
方法 在动物实验中，SD雄性大鼠40只，体重250~270 g，随机分成四组：假手术组（S组）、缺血-再灌注组（IR组）、二甲基亚砜 (DMSO)+缺血-再灌注组(DIR组)和吡格列酮+缺血-再灌注组(PIR组)。其中S组进行假手术处理，IR组进行脑中动脉缺血(MCAO)建模处理，DIR组给予DMSO，随后进行MCAO造模处理。PIR组给予吡格列酮，随后进行MCAO造模处理。在细胞实验中，通过慢病毒转染BV2细胞使PPAR-γ过表达，将细胞培养孔随机分为三组：空白对照组（B组）、阴性对照组（L1组）、过表达组（L2组）。其中B组未做处理，L1组转染PPAR-γ阴性病毒，L2组转染PPAR-γ阳性病毒。之后将细胞培养孔随机分为四组：正常对照组（C组）、正常细胞+LPS处理组（L组）、阴性对照+LPS处理组（LL1组）和过表达+LPS处理组（LL2组）。其中C组未做处理，L组用LPS处理，LL1组转染阴性病毒并确定转染率后使用LPS处理，LL2组转染阳性病毒并确定转染率后用LPS处理。各组大鼠使用Zea Longa评分标准进行神经行为学评分，TTC染色比较脑梗死容积百分比大小，采用ELISA法检测四组大鼠和四组BV2细胞IL-1β和IL-18浓度，Western blot法检测PPAR-γ、活化的半胱天冬酶1（caspase-1）和NOD样受体家族3（NLRP3）蛋白相对含量。
结果 与IR组比较，PIR组大鼠行为学评分明显降低，脑梗死容积百分比明显减小，PPAR-γ的蛋白相对含量明显增高，活化的caspase-1、NLRP3蛋白相对含量明显降低，IL-1β和IL-18浓度明显降低（P<0.05）。与B组比较，L2组的PPAR-γ蛋白相对含量明显增高。与C组比较，LL2组活化的caspase-1和NLRP3蛋白相对含量明显升高（P<0.05），IL-1β和IL-18浓度明显升高（P<0.05）。
结论 吡格列酮通过激活PPAR-γ减轻脑缺血-再灌注损伤，其机制是通过激活PPAR-γ，抑制NLRP3的表达，减轻炎症反应，进而使可能存在的caspase-1介导的细胞焦亡减少。 |
| 英文摘要: |
Objective To investigate the effect of PPAR-γ activation on cerebral ischemia-reperfusion injury (CIRI) and lipopolysaccharide (LPS) induced cell inflammation.
Methods Forty male SD rats, weighing 250-270 g, were randomly divided into 4 groups: sham group (group S), ischemia-reperfusion group (group IR), DMSO+ischemia-reperfusion group (group DIR) and pioglitazone+ischemia-reperfusion group (group PIR). BV2 cells transfected with lentivirus that overexpressed PPAR-γ were randomly divided into 3 groups: blank group (group B), negative-control group (group L1), and overexpression group (group L2). BV2 cells were then randomly divided into 4 groups: control group (group C), BV2+LPS group (group L), LV- +LPS group (group LL1) and LV+ +LPS group (group LL2). Neurological deficit scores were recorded in each group by using Zea Longa standard, and cerebral infarct volume percentage was measured by TTC staining. The expression of PPAR-γ, active caspase-1 and NLRP3 were detected by western blot, and the content of IL-1β and IL-18 were detected by ELISA in rats and BV2 cells.
Results Compared with the group IR, the behavioral score of the group PIR was significantly reduced,the level of PPAR-γ in group PIR was significantly increased. Moreover, pioglitazone notably decreased infarct volume percentage and inhibited the level of NLRP3 and caspase-3 activation, as well as the content of IL-1β and IL-18 (P < 0.05). Compared with group B, the relative level of PPAR-γ protein in group L2 was significantly increased. Compared with group C, the levels of active caspase-1, NLRP3, IL-1β and IL-18 in group LL2 were significantly increased (P < 0.05).
Conclusion Pioglitazone relieved cerebral ischemia-reperfusion injury by the mechanisms involving in inhibiting NLRP3 activation，reduce inflammation，and subsequently reducing thepossible caspase-1-dependent pyroptosis through activating PPAR-γ. |
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