PPARγ激动剂吡格列酮对创伤性脑损伤的神经保护作用及量效关系的研究

发布时间：2018-04-09 09:49

本文选题：TBI　切入点：PPARγ　出处：《重庆医科大学》2014年硕士论文

【摘要】：目的：通过测定大脑皮层炎症因子TNF-α mRNA、IL-6mRNA及PPARγ mRNA的表达，观察大脑皮层迟发性神经损伤和细胞凋亡情况，研究PPARγ激动剂吡格列酮对创伤性脑损伤的神经保护作用及量效关系。方法：利用改良的Feeney自由落体损伤装置制作脑损伤大鼠模型，实验大鼠随机分组：正常组、假手术组、吡格列酮组（在损伤后6h,12h,24,30h,36h,42h分别注射不同剂量的吡格列酮，包括0.5mg/kg pio组、1.0mg/kg pio组、10mg/kg pio组）、创伤对照组（在创伤后相同时间注射同样剂量的生理盐水）、1mg/kg T0070907（在创伤后相同时间注射1mg/kg的T0070907）、T0070907+1.0mg/kg pio（在创伤前半小时注射1mg/kg T0070907，吡格列酮在相同时间注射1mg/kg），48h后通过定量PCR检测PPARγ、TNF、IL-6基因mRAN的表达；用HE、Nissl及TUNEL染色方法，测定实验大鼠创伤脑皮层周围神经元迟发性死亡和神经细胞凋亡程度。结果：1）TBI后48h qPCR测得：与正常组和假致伤组相比，对照组TNF-α mRNA、IL-6mRNA表达量明显增高(P0.01)；与对创伤照组相比，不同剂量吡格列酮组随着吡格列酮剂量的增加TNF-α mRNA、IL-6mRNA表达量依次降低（P0.01）。2）T0070907+1mg pio组与1mgpio组相比，TNF-α mRNA、IL-6mRNA的表达明显增加（P0.05）。3）与对照组相比，只有10mg pio组PPARγ mRNA表达明显增加(P0.01)。4）TBI后48h HE、NISSL、TUNEL染色观察到：与正常组和假致伤组相比，创伤对照组神经细胞损伤，，尼氏体脱失细胞数及凋亡明显增加（P0.01）;与创伤对照组相比，不同剂量吡格列酮组随着吡格列酮剂量的增加神经细胞损伤、尼氏体脱失细胞数及凋亡依次减轻（P0.01）；T0070907+1.0mg pio组和1.0mg pio组相比,神经细胞损伤明显加重（P0.01）。结论：吡格列酮可减轻TBI后炎症反应，减轻神经细胞的损伤和凋亡，对TBI具有神经保护作用；并且这种作用呈现剂量依赖性。
[Abstract]:Objective: to study the neuroprotective effect and dose-effect relationship of PPAR 纬 agonist pioglitazone on traumatic brain injury by measuring the expression of TNF- 伪 mRNA-IL-6 mRNA and PPAR 纬 mRNA in cerebral cortex, and observing the delayed nerve injury and apoptosis of cerebral cortex.Methods: the rat model of brain injury was made by using the modified Feeney free fall injury device. The rats were randomly divided into normal group, sham operation group and pioglitazone group (at 6 h after injury), pioglitazone was injected with different doses of pioglitazone at 24 h, 24 h, 30 h, 36 h and 42 h after injury, and the rats were randomly divided into three groups: normal group, sham-operated group and pioglitazone group.It includes 0.5mg/kg pio group, 1.0 mg / kg pio group, 10 mg / kg pio group, trauma control group (1 mg / kg normal saline injection at the same time after trauma) (1mg/kg T0070907 1.0mg/kg Pio at the same time after trauma) (1mg/kg T0070907 at half hour before trauma, pioglitazone at the same time after trauma).At the same time, the expression of PPAR 纬 -TNF-IL-6 gene mRAN was detected by quantitative PCR 48 h after injection of 1 mg 路kg ~ (-1) 路L ~ (-1) 路L ~ (-1);The degree of delayed death and neuronal apoptosis in the peripheral neurons of traumatic cerebral cortex in experimental rats was determined by Hep Nissl and TUNEL staining.Results the expression of TNF- 伪 mRNA-IL-6 mRNA in the control group was significantly higher than that in the normal group and the sham injury group 48 h after TBI, and the expression of IL-6 mRNA in the control group was significantly higher than that in the trauma exposure group, and the expression of IL-6 mRNA in the control group was significantly higher than that in the injury exposure group.Only in the 10mg pio group, the expression of PPAR 纬 mRNA increased significantly 48 hours after the injury, and the number and apoptosis of neuronal cells in the injured control group increased significantly compared with the normal group and the sham injured group, and compared with the trauma control group, the expression of PPAR 纬 mRNA increased significantly in the 10mg pio group, and compared with that in the trauma control group, it was found that the number of neuronal cells in the injured control group was significantly higher than that in the injured control group.With the increase of pioglitazone dosage, the number and apoptosis of the cells lost in the Nissl body decreased in turn. Compared with the 1.0mg pio group, the nerve cell damage in the pioglitazone group was significantly increased than that in the P0.01T0070907 1.0mg pio group.Conclusion: pioglitazone can attenuate the inflammatory reaction after TBI, reduce the injury and apoptosis of nerve cells, and has neuroprotective effect on TBI in a dose-dependent manner.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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