Chang Chih-Zen, Wu Shu-Chuan, Kwan Aij-Lie
Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
J Vasc Res. 2015;52(1):12-21. doi: 10.1159/000381099. Epub 2015 Apr 16.
The peroxisome proliferator-activated receptor (PPAR) is downregulated in the cortex of experimental subarachnoid hemorrhage (SAH) animals. This study is to examine the effect of glycyrrhizin on the alternation of PPARs and proinflammatory cytokines in a rodent SAH model. CSF cytokines were evaluated by RT-PCR. Basilar arteries (BAs) were harvested to examine PPARs (RT-PCR and Western blot), and a morphological examination was conducted. Deformed endothelium and tortuous elastic lamina were observed in the BAs of the SAH groups, but they were absent in the glycyrrhizin groups or the healthy controls. The PPAR-γ and -δ protein levels were reduced in the SAH groups (p < 0.01). Glycyrrhizin significantly increased the expressed PPAR-γ protein and mRNA (preconditioning) and PPAR-δ mRNA (both treatment and preconditioning), which corresponded to the reduced IL-1β and TNF-α levels. The administration of a PPAR-γ inhibitor, BADGE, halted the reduction of IL-1β and TNF-α in the glycyrrhizin groups. Conclusively, glycyrrhizin exerts anti-inflammatory effects on SAH-induced vasospasm and attenuates the expression of PPARs, especially PPAR-γ, which corresponds to the severity of SAH-related inflammation. These findings also offer credit to the antivasospastic effect of glycyrrhizin and its vasculoprotective effect in animals subjected to SAH.
过氧化物酶体增殖物激活受体（PPAR）在实验性蛛网膜下腔出血（SAH）动物的皮质中表达下调。本研究旨在探讨甘草酸对啮齿类动物SAH模型中PPARs和促炎细胞因子变化的影响。通过逆转录聚合酶链反应（RT-PCR）评估脑脊液细胞因子。采集基底动脉（BAs）以检测PPARs（RT-PCR和蛋白质印迹法），并进行形态学检查。在SAH组的BAs中观察到内皮变形和弹性膜迂曲，但在甘草酸组或健康对照组中未观察到。SAH组中PPAR-γ和-δ蛋白水平降低（p<0.01）。甘草酸显著增加了PPAR-γ蛋白和mRNA的表达（预处理）以及PPAR-δ mRNA的表达（治疗和预处理），这与白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平降低相对应。给予PPAR-γ抑制剂BADGE可阻止甘草酸组中IL-1β和TNF-α的降低。总之，甘草酸对SAH诱导的血管痉挛具有抗炎作用，并减弱PPARs的表达，尤其是PPAR-γ，这与SAH相关炎症的严重程度相对应。这些发现也证实了甘草酸在SAH动物中的抗血管痉挛作用及其血管保护作用。
