天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (1): 34-37.doi: 10.11958/20192153

• 实验研究 • 上一篇    下一篇

大鼠脑缺血再灌注早期过氧化物酶体增殖物激活受体γ 活化与细胞焦亡的关系

刘海颖，冯子人，孙辉，孟爱国△，赵俊暕，张文婷   

  1. 基金项目：河北省高等学校科学技术研究重点项目（ZD2019050） 作者单位：华北理工大学附属医院检验科，唐山市医学分子检验与诊断重点实验室（邮编063000） 作者简介：刘海颖（1992），女，硕士在读，主要从事脑缺血再灌注损伤机制研究 △通讯作者 E-mail: tangshan201501@sina.cn
  • 收稿日期:2019-07-15 修回日期:2019-10-25 出版日期:2020-01-15 发布日期:2020-01-15
  • 通讯作者: 孟爱国 E-mail:tangshan201501@sina.cn
  • 基金资助:
    microRNA-124/STAT3通路调控大鼠脑缺血再灌注损伤中细胞自噬及焦亡的机制

The relationship between PPAR gamma activation and pyroptosis in the early stage of cerebral ischemia-reperfusion in rats

LIU Hai-ying, FENG Zi-ren, SUN Hui, MENG Ai-guo△, ZHAO Jun-jian, ZHANG Wen-ting   

  1. North China University of Science and Technology Affiliated Hospital, Key Laboratory of Medical Molecular Testing and Diagnosis in Tangshan, Tangshan 063000, China △Corresponding Author E-mail: tangshan201501@sina.cn
  • Received:2019-07-15 Revised:2019-10-25 Published:2020-01-15 Online:2020-01-15

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摘要： 目的 探讨过氧化物酶体增殖物激活受体γ（PPARγ）活化在大鼠脑缺血再灌注损伤中与细胞焦亡的关 系。方法 40只SPF级雄性SD 大鼠随机分为假手术组（sham组）、模型组（MCAO组）、给药组（PGZ组、PGZ+GW9662 组），每组10只；采用Zea-Longa评分法进行神经功能评分，TTC染色测量脑梗死面积，运用Western blot 技术分析大 鼠脑组织中PPARγ，焦亡关键蛋白半胱氨酸天冬氨酸蛋白酶-1（caspase-1）、Gasdermin D（GSDMD）及炎症因子白细 胞介素-1β（IL-1β）、白细胞介素-18（IL-18）的表达变化。结果 与 sham 组比较，缺血再灌注 24 h 后 MCAO 组中 PPARγ 表达明显降低（P＜0.05），焦亡关键蛋白 caspase-1、GSDMD 及炎症因子 IL-1β、IL-18 水平显著增高（P＜ 0.05），神经功能评分明显增加，脑梗死面积增大（P＜0.01）；与MCAO组比较，PGZ组中PPARγ显著升高（P＜0.05）， 焦亡关键蛋白caspase-1、GSDMD及炎症因子IL-1β、IL-18水平降低（P＜0.05），神经功能评分显著下降，脑梗死面积 减少（P＜0.01）；而PGZ+GW9662组中，PPARγ的作用被逆转。结论 在脑缺血再灌注损伤早期PPARγ激活可通过 抑制细胞焦亡产生从而减轻神经细胞损伤。

关键词: 再灌注损伤, 细胞焦亡, 脑损伤, PPARγ, 吡格列酮

Abstract: Objective To investigate the relationship between peroxisome proliferator activated receptor γ (PPARγ) activation and pyroptosis in rat model of cerebral ischemia-reperfusion injury. Methods Forty male SD rats of SPF were randomly divided into sham operation group, MCAO model group, pioglitazone group and pioglitazone+GW9662 group, 10 rats for each group. Neurological deficits were measured by Zea-Longa score, and infarct sizes were measured by TTC staining. The expressions of PPARγ, caspase-1, Gasdermin D (GSDMD), interleukin (IL) - 1β and IL-18 in ischemic penumbra were observed by Western blot assay. Results The expression level of PPARγ protein was significantly lower 24- h after cerebral ischemia-reperfusion injury in MCAO group than that of sham group (P＜0.05). The values of caspase-1, GSDMD, IL-1β and IL-18 were significantly higher in MCAO group than those in sham operation group (P＜0.05). Meanwhile, the neurological deficits and infarct sizes were significantly higher in MCAO group than those of sham operation group (P＜0.01). The level of PPARγ was significantly increased in PGZ group compared with that of MCAO group (P＜ 0.05), while the caspase-1, GSDMD, IL-1β and IL-18 decreased (P＜0.05). And neurological deficits and infarct sizes decreased significantly (P＜0.01). However, in PGZ+GW9662 group, the effect of PPARγ was reversed. Conclusion At the early stage of rat cerebral ischemia/reperfusion, the activation of PPARγ inhibits the pyroptosis to reduce neuron injury.

Key words: reperfusion injury, pyroptosis, brain injuries, PPAR gamma, Pioglitazone