鞘内注射PPARγ激动剂Pioglitazone对神经病理性疼痛大鼠痛行为及星形胶质细胞活性的影响  

Effects of Intrathecal Injection PPARγAgonist Pioglitazone on the Pain Behavior and Astrocyte Activity in Rats with Neuropathic Pain

作　　者：黄彤虹 凌国栩 钟妤[1] HUANG Tong-hong;LING Guo-xu;ZHONG Yu(Department of Anesthesia,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学第一附属医院麻醉科,广西南宁530021

出　　处：《医学信息》2023年第7期85-89,共5页Journal of Medical Information

基　　金：广西自然科学基金项目(编号:2015GXNSFAA139154、2017GXNSFBA198039)。

摘　　要：目的观察鞘内注射PPARγ激动剂Pioglitazone对神经病理性疼痛大鼠痛行为及星形胶质细胞活性的影响。方法将220~250 g的雄性SPF级SD大鼠64只按随机数字表法分为4组:Sham+DMSO组(二甲基亚砜,S+D组)、Sham+Pioglitazone组(S+P组)、CCI+DMSO组(I+D组)、CCI+Pioglitazone组(I+P组)。通过结扎大鼠坐骨神经致慢性压迫性损伤(CCI)建立神经病理性疼痛模型。从CCI术后第3天开始鞘内注射相应药物至术后第14天。于术前及术后第3、7、14、21天检测大鼠右后爪机械缩足阈值(PWMT)和热缩足反射潜伏期(PWTL),并于术后第14天取大鼠脊髓腰膨大部,采用免疫印迹法测定脊髓背角星形胶质细胞标记物GFAP蛋白表达,采用ELISA检测炎性因子TNF-α、IL-1β和IL-6表达。结果S+D组、S+P组术后第3、7、14、21天PWMT、PWTL与术前比较,差异无统计学意义(P>0.05);I+D组和I+P组术后第3、7、14、21天PWMT和PWTL值低于术前(P<0.05);S+P组术后第3、7、14、21天PWMT和PWTL值与S+D组比较,差异无统计学意义(P>0.05);I+D组和I+P组术后第3、7、14、21天PWMT和PWTL值低于S+D组(P<0.05);I+P组术后第3、7、14天PWMT和PWTL高于I+D组(P<0.05)。S+D组和S+P组GFAP蛋白和TNF-α、IL-1β、IL-6表达比较,差异无统计学意义(P>0.05);I+D组和I+P组GFAP蛋白和TNF-α、IL-1β、IL-6表达高于S+D组和S+P组(P<0.05),而I+P组GFAP蛋白和TNF-α、IL-1β、IL-6表达低于I+D组(P<0.05)。结论鞘内注射Pioglitazone能缓解神经病理性疼痛模型大鼠的机械痛和热痛行为,其机制可能与抑制脊髓背角星形胶质细胞的活性,进而抑制炎性因子TNF-α、IL-1β和IL-6的释放有关。Objective To investigate the effects of intrathecal injection PPARγagonist Pioglitazone on the pain behavior and astrocyte activity in rats with neuropathic pain.Methods Sixty-four male adult Sprague-Dawley rats of 220-250 g were randomly divided into 4 groups:Sham+DMSO group(dimethyl sulfoxide,S+D group),Sham+Pioglitazone(S+P)group,CCI+DMSO(I+D)group,CCI+Pioglitazone(I+P)group.The rat model of neuropathic pain was established by chronic sciatic nerve ligation(CCI).The homologous drugs were injected intrathecally from the third day after CCI for 14 days.The paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)of the right hind paw were measured before operation and on the 3rd,7th,14th and 21st day after operation.The lumbar enlargement of the spinal cord was taken on the 14 th day after operation.The expression of astrocyte marker GFAP protein in the spinal dorsal horn was determined by Western blotting,and the expression of inflammatory factors TNF-α,IL-1βand IL-6 was detected by ELISA.Results There was no significant difference in PWMT and PWTL between before operation and on the 3rd,7th,14th and 21st day after operation in S+D group and S+P group(P>0.05).The values of PWMT and PWTL in I+D group and I+P group on the 3rd,7th,14th and 21st day after operation were lower than those before operation(P<0.05).There was no significant difference in PWMT and PWTL between S+P group and S+D group on the 3rd,7th,14th and 21st day after operation(P>0.05).The values of PWMT and PWTL in I+D group and I+P group were lower than those in S+D group on the 3rd,7th,14th and 21st day after operation(P<0.05).The PWMT and PWTL in I+P group were higher than those in I+D group a on the 3rd,7th,14th day after operation(P<0.05).There was no significant difference in the expression of GFAP protein and TNF-α,IL-1βand IL-6 between S+D group and S+P group(P>0.05).The expression of GFAP protein and TNF-α,IL-1βand IL-6 in I+D group and I+P group were higher than those in S+D group and S+P group(P<0.05),while

关 键 词：神经病理性疼痛 过氧化物酶体增殖物激活受体Γ 星形胶质细胞 胶质纤维酸性蛋白 炎性因子 

分 类 号：R441.1[医药卫生—诊断学]