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

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。

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

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 wererandomly divided into sham operation group, MCAO model group, pioglitazone group and pioglitazone+GW9662 group, 10rats for each group. Neurological deficits were measured by Zea-Longa score, and infarct sizes were measured by TTCstaining. The expressions of PPARγ, caspase-1, Gasdermin D (GSDMD), interleukin (IL) - 1β and IL-18 in ischemicpenumbra 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 operationgroup (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 sizesdecreased significantly (P＜0.01). However, in PGZ+GW9662 group, the effect of PPARγ was reversed. Conclusion Atthe early stage of rat cerebral ischemia/reperfusion, the activation of PPARγ inhibits the pyroptosis to reduce neuron injury.