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

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

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。

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.