低剂量吡格列酮对创伤性脑损伤神经保护的作用途径 - 第三军医大学学报.docVIP

低剂量吡格列酮通过非PPARγ依赖途径保护创伤性脑损伤 胡琴琴11 ，邓永兵22，刘先俊31，毛成毅41，3，蒋雪51* （1重庆医科大学 基础医学院 生物化学与分子生物学教研室，重庆，400016；2重庆市急救医疗中心神经外科，重庆，400014；3重庆市第三军医大学 大坪医院 野战外科研究所 病理科，重庆，400042；） 摘要:目的 探讨低剂量吡格列酮（Pio）是否通过非PPARγ依赖途径对创伤性脑损伤发挥神经保护作用。方法 6周龄SD雄性大鼠30只随机分为假致伤组、TBI组、PPARγ拮抗剂0 mg/kg组、低剂量Pio 1.0mg/kg组、T0070907 1.0 mg/kg+ Pio 1.0 mg/kg组、大剂量Pio10 mg/kg组，除假致伤组外均作Feeney自由落体重物锤打击。采用HE染色、尼氏染色及TUNEL染色观察实验大鼠脑组织细胞损伤、尼氏体脱失及神经细胞凋亡程度,定量PCR技术检测PPARγmRNA表达水平。结果 (1) 低剂量吡格列酮能减轻创伤性脑损伤后细胞损伤；( 2) 低剂量吡格列酮能减轻创伤性脑损伤后尼氏体脱失；(3) 低剂量吡格列酮能减轻创伤性脑损伤后细胞凋亡；(4) 低剂量吡格列酮不能激活PPARγ受体。结论 低剂量吡格列酮可通过非PPARγ依赖途径对创伤性脑损伤发挥神经保护作用。 关键词：创伤性脑损伤；吡格列酮； 非PPARγ依赖途径；神经保护 中图分类号：R651.15 文献标识码：A Low-dose Pioglitazone Protects Traumatic Brain Injury through PPARγ-independent Pathway HU Qin-qin1, DENG Yong-bing2, LIU Xian-jun1, MAO Cheng-yi1,3, JIANG Xue1* (1. Department?of?Biochemistry and?Molecular?Biology, Chongqing?Medical?University, Chongqing, 400016, China; 2 .Department of Neurosurgery, Chongqing Emergency Medical Center, Chongqing, 400014, China; 3.Field?Surgery Institute?of?Pathology, Daping?Hospital,?Third?Military Medical?University,?Chongqing,? 400042, China) Abstract: Objective To observe whether low-dose Pioglitazone can exert neuroprotection through the PPARγ-independent pathway after traumatic brain injury. Methods Thirty six-week-old male SD rats were randomly divided into sham-injured group, TBI group, T0070907 (antagonist of PPARγ) group, low-dose Pioglitazone group (1.0mg/kg), T0070907 (1.0mg/kg) and Pioglitazone (1.0mg/kg) co-administrated group, high-dose Pioglitazone group (10.0 mg/kg). TBI models were established by Feeney’s free falling method except sham-injured group. HE, Nissl, TUNEL’s staining were used to observe the cellular changes, the loss of Nissl?body, and the apoptosis of neuronal?cell in the brain tissue of experimental rats, and the expression of PPARγ in brain tissue was detected by RT-PCR. Results (1) Cellular damage caused by TBI could be reduced after treatment of low-d