Peroxisome-proliferator activator receptor γ (PPARγ) has an anti-inflammatory role that inhibits the nuclear factor-κB (NF-κB) pathway and regulates the expressions of pro-inflammatory proteins, whereas its role in parasitic meningoencephalitis remains unknown. In this study we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by the rat lungworm Angiostrongylus cantonensis. We observed increased protein NF-κB expression in mouse brain tissue using GW9662, which is the specific antagonist of PPARγ, in a mouse model of angiostrongyliasis. Then we investigated NF-κB-related downstream proteins, such as COX-2, NOSs, and IL-1β, with Western blot or enzyme-linked immunosorbent assay and found that the protein expression was upregulated. The results of gelatin zymography also showed that the MMP-9 activities were upregulated. Treatment with GW9662 increased the permeability of the blood-brain barrier and the number of eosinophils in cerebrospinal fluid. These results suggested that in angiostrongyliasis, PPARγ may play an anti-inflammation role in many inflammatory mediators, including NOS-related oxidative stress, cytokines, and matrix metalloproteinase cascade by decreasing the NF-κB action.

过氧化物酶体增殖物激活剂受体γ（PPARγ）具有抑制核因子-κB（NF-κB）通路并调节促炎蛋白表达的抗炎作用，但在寄生性脑膜脑炎中的作用仍未知。在这项研究中，我们研究了PPARγ及其在大鼠肺虫广州管圆线虫引起的嗜酸性脑膜脑炎中的作用及其机制。。我们观察到在毛细血管平滑肌病的小鼠模型中，使用GW9662（PPARγ的特异性拮抗剂）在小鼠脑组织中增加了蛋白质NF-κB的表达。然后，我们用Western blot或酶联免疫吸附法研究了NF-κB相关的下游蛋白，例如COX-2，NOS和IL-1β，发现该蛋白的表达上调。明胶酶谱分析的结果还表明，MMP-9活性被上调。GW9662的治疗增加了脑脊液中血脑屏障的通透性和嗜酸性粒细胞的数量。这些结果表明，在血管新生病中，PPARγ可能通过降低NF-κB的作用在许多炎症介质中发挥抗炎作用，包括与NOS相关的氧化应激，细胞因子和基质金属蛋白酶级联反应。