本文選題：TBI　切入點：PPARγ　出處：《重慶醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：通過測定大腦皮層炎癥因子TNF-α mRNA、IL-6mRNA及PPARγ mRNA的表達，觀察大腦皮層遲發(fā)性神經(jīng)損傷和細胞凋亡情況，研究PPARγ激動劑吡格列酮對創(chuàng)傷性腦損傷的神經(jīng)保護作用及量效關(guān)系。 方法：利用改良的Feeney自由落體損傷裝置制作腦損傷大鼠模型，實驗大鼠隨機分組：正常組、假手術(shù)組、吡格列酮組（在損傷后6h,12h,24,30h,36h,42h分別注射不同劑量的吡格列酮，包括0.5mg/kg pio組、1.0mg/kg pio組、10mg/kg pio組）、創(chuàng)傷對照組（在創(chuàng)傷后相同時間注射同樣劑量的生理鹽水）、1mg/kg T0070907（在創(chuàng)傷后相同時間注射1mg/kg的T0070907）、T0070907+1.0mg/kg pio（在創(chuàng)傷前半小時注射1mg/kg T0070907，吡格列酮在相同時間注射1mg/kg），48h后通過定量PCR檢測PPARγ、TNF、IL-6基因mRAN的表達；用HE、Nissl及TUNEL染色方法，測定實驗大鼠創(chuàng)傷腦皮層周圍神經(jīng)元遲發(fā)性死亡和神經(jīng)細胞凋亡程度。 結(jié)果：1）TBI后48h qPCR測得：與正常組和假致傷組相比，對照組TNF-α mRNA、IL-6mRNA表達量明顯增高(P0.01)；與對創(chuàng)傷照組相比，不同劑量吡格列酮組隨著吡格列酮劑量的增加TNF-α mRNA、IL-6mRNA表達量依次降低（P0.01）。2）T0070907+1mg pio組與1mgpio組相比，TNF-α mRNA、IL-6mRNA的表達明顯增加（P0.05）。3）與對照組相比，只有10mg pio組PPARγ mRNA表達明顯增加(P0.01)。4）TBI后48h HE、NISSL、TUNEL染色觀察到：與正常組和假致傷組相比，創(chuàng)傷對照組神經(jīng)細胞損傷，，尼氏體脫失細胞數(shù)及凋亡明顯增加（P0.01）;與創(chuàng)傷對照組相比，不同劑量吡格列酮組隨著吡格列酮劑量的增加神經(jīng)細胞損傷、尼氏體脫失細胞數(shù)及凋亡依次減輕（P0.01）；T0070907+1.0mg pio組和1.0mg pio組相比,神經(jīng)細胞損傷明顯加重（P0.01）。 結(jié)論：吡格列酮可減輕TBI后炎癥反應(yīng)，減輕神經(jīng)細胞的損傷和凋亡，對TBI具有神經(jīng)保護作用；并且這種作用呈現(xiàn)劑量依賴性。
[Abstract]:Objective: to study the neuroprotective effect and dose-effect relationship of PPAR 緯 agonist pioglitazone on traumatic brain injury by measuring the expression of TNF- 偽 mRNA-IL-6 mRNA and PPAR 緯 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 緯 -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- 偽 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 緯 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 緯 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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965

【參考文獻】

相關(guān)期刊論文 前1條

1 喬保華;高建新;王芬;邴國英;;PPARγ激動劑吡格列酮減少大鼠創(chuàng)傷性腦損傷后的神經(jīng)損傷和膠質(zhì)增殖[J];中國病理生理雜志;2010年05期

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