吡格列酮对大鼠创份性脑损伤后炎症因子抑制作用的研究

摘要

Objective To observe the effects of peroxisome proliferator activated receptor-γ (PPAR-γ) and its activator pioglitazone on the expression of the inflammatory cytokines after traumatic brain injury (TBI) in rats and explore its mechanism. Methods Adult SD rats were randomized into normal control (n=10), sham-operated (n=10), TBI model (n=12) and pioglitazone treatment (n=12) groups. Impact brain injury was induced in the later two groups and 18 h after the injury, normal saline and pioglitazone at the daily dose of 20 mg/kg were given, respectively. The rats in the sham-operated group received identical treatment to the model group but without TBI. Seven days later, the brain tissue was collected and the cerebral water contents were measured. RT-PCR and Western blot were performed to detect the mRNA and protein expressions of PPAR-γ, regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). Results Cerebral water content of the TBI model group was markedly increased as compared with that of the control and sham-operated groups (P<0.05). The expressions of PPAR-γ, RANTES and MIF significantly increased after TBI, and pioglitazone treatment resulted in further activation of PPAR-γ but markedly down-regulated RANTES and MIF expressions (P<0.05). Conclusion Pioglitazone offers protective effect against sustained brain edema and inflammation after TBI possibly by lowering the expressions of such inflammatory cytokines as RANTES and MIF in the brain tissue.%目的 探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)及其激活剂噻唑烷二酮类药物--吡格列酮对创伤性脑损伤(TBI)大鼠模型脑组织中正常T细胞活化后表达和分泌的调节蛋白(RANTES)、巨噬细胞移动抑制因子(MIF)表达的影响. 方法成年SD大鼠按照随机数字表法分为正常对照组(10只)、假手术组(10只)、TBI模型组(12只)及吡格列酮治疗组(12只).后两组采用改进的Feeney自由落体脑损伤装置制作TBI大鼠模型.伤后18 h分别给予生理盐水及20mg/(kg·d)吡格列酮治疗:假手术组不进行自由落体致伤,其余步骤同上,术后给与生理盐水治疗;正常对照组不进行任何处理.7 d后收集各组大鼠脑组织,计算脑组织含水量,并采用RT-PCR及Westernblot法检测各组PPAR-γ、RANTES及MIF的mRNA、蛋白表达差异. 结果与对照组及假手术组相比,TBI损伤组大鼠脑组织含水量明显增加,且PPAR-γmRNA表达明显增强,同时RANTES、MIF mRNA及蛋白表达也明显上调;而吡格列酮治疗组大鼠脑组织PPAR-γ的表达进一步增加,RANTES及MIF表达则有所下降. 结论吡格列酮对减轻创伤性脑损伤后持续存在的炎症反应及脑水肿具有一定作用,其机制可能与降低脑组织中RANTES及MIF等炎性细胞因子含量有关.