吡格列酮通过上调PPARγ降低创伤性脑损伤大鼠脑组织炎性细胞因子的水平

Pioglitazone decreases the levels of inflammatory cytokines in SD rats with traumatic brain injury via up-regulating PPARγ

目的观察吡格列酮对创伤性脑损伤(TBI)大鼠过氧化物酶体增殖物激活受体γ(PPARγ)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)mRNA的表达影响及量效关系。方法 72只SD雄性大鼠随机分为正常组、假手术组、对照组、(0.5、1.0、10.0)mg/kg吡咯列酮组,每组各12只。改良Feeney法制作TBI模型,假手术组只开孔不进行打击处理,治疗组按体质量分别给予(0.5、1.0、10.0)mg/kg吡咯列酮治疗,对照组和假手术组给等量安慰剂。致伤24、48 h后,采用反转录PCR检测脑损伤部位组织PPARγ、TNF-α、IL-6的mRNA水平。结果损伤24 h后,各吡格列酮组PPARγmRNA表达量显著上调,不同剂量吡咯列酮组间PPARγmRNA表达量差异显著,有剂量依赖性;损伤后治疗组TNF-αmRNA的表达量显著下调,24 h后,与0.5 mg/kg组相比,(1.0、10.0)mg/kg吡咯列酮组TNF-α、IL-6的mRNA水平降低。结论吡格列酮上调TBI大鼠PPARγmRNA、下调TNF-α和IL-6 mRNA表达,抑制炎症反应。

Objective To observe the effect of pioglitazone on the levels of peroxisome proliferator activated receptor γ（ PPARγ）,tumor necrosis factor-α（ TNF-α） and interleukin 6（ IL-6） mRNAs and the dose-dependent relationship in rats with traumatic brain injury（ TBI）. Methods A total of 72 male SD rats were randomly divided into a normal group,a sham operation group,a control group and three pioglitazone groups receiving doses of 0. 5,1. 0 and 10. 0 mg/kg,with 12 rats in each group. Modified Feeney＇s free falling method was used to make TBI models; the sham operation group only had an operation but without combat; the pioglitazone groups were given pioglitazone at the doses of 0.5,1.0 and 10.0 mg/kg,respectively;the control group and sham operation group were given equal amount of placebo. The levels of PPARγ,TNF-α and IL-6mRNAs in lesion brain tissues were detected by reverse transcription PCR 24 and 48 hours after injury. Results Twenty-four hours after the injury,the expression of PPARγ mRNA was up-regulated significantly in all pioglitazone groups,with significant difference between each pioglitazone group in a dose-dependent manner. The expression of TNF-α mRNA was significantly down-regulated in the treatment groups after injury. Twenty-four hours after the injury,the levels of TNF-α and IL-6 mRNAs in the pioglitazone groups receiving the doses of 1. 0 and 10. 0 mg/kg decreased compared with those in the group receiving 0. 5 mg/kg pioglitazone. Conclusion Pioglitazone inhibits inflammatory reaction by up-regulating the level of PPARγ mRNA and down-regulating the levels of TNF-α and IL-6 mRNAs in rats with TBI.