盐酸椒苯酮胺对耳蜗缺血再灌注后白介素-1β、肿瘤坏死因子-α mRNA 及Fas蛋白表达的影响  

Effect of piperphentonamine hydrochloride on expressions of interleukin-1β and TNF-α mRNA and Fas protein in guinea pigs with cochlear ischemia/reperfusion injury

作　　者：李永贺[1] 吴剑[1] 李威[1] 陈浩[1] 万良财[1] 

机构地区：[1]南方医科大学珠江医院耳鼻咽喉一头颈外科,广东广州510282

出　　处：《南方医科大学学报》2013年第11期1669-1672,1677,共5页Journal of Southern Medical University

基　　金：广东省教育部产学研结合项目(2010B090400421)

摘　　要：目的探讨豚鼠耳蜗白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA、Fas蛋白表达与耳蜗缺血再灌注损伤关系及盐酸椒苯酮胺(PPTA)对豚鼠耳蜗缺血再灌注损伤保护机制。方法豚鼠64只随机分为4组,每组16只,分别为正常组、空白对照组、缺血再灌注对照组和缺血再灌注PPTA组,每组随机选6只用于RT-PCR检测,剩余10只用于免疫组化。微血管夹夹闭双侧椎动脉及右侧颈总动脉1 h松开动脉夹以制造耳蜗缺血模型,缺血再灌注PPTA组于缺血1 h再灌注后立即经股静脉注射PPTA(10 mg/kg),缺血再灌注对照组注射等量生理盐水,24 h后取标本。用RT-PCR法检测IL-1β和TNF-α的mRNA的表达。结果缺血再灌注对照组耳蜗组织IL-1β、TNF-αmRNA表达量显著高于正常组和空白对照组(P<0.001);缺血再灌注PPTA组耳蜗组织IL-1βmRNA、TNF-αmRNA表达量显著低于缺血再灌注对照组(P<0.001);缺血再灌注组Corti器、螺旋神经节和血管纹Fas表达阳性,积分光密度值(IOD)值较其它三组明显增高(P<0.05),缺血再灌注PPTA干预组IOD值与正常组及空白对照组差异无统计学意义(P>0.05)。结论 PPTA可抑制缺血再灌注耳蜗各部位IL-1β、TNF-αmRNA、Fas蛋白表达;PPTA可能通过抑制炎性反应及抑制细胞凋亡实现对耳蜗缺血再灌注损伤的拮抗作用。Objective To investigate the relationship between IL-1β and TNF-α mRNA and Fas protein expressions and cochlear ischemia reperfusion injury and investigate the protective mechanism of PPTA against cochlear reperfusion injury. Methods Sixty-four guinea pigs were randomly divided into normal control group, blank control group, ischemia/reperfusion （by clamping the bilateral vertebral artery and right common carotid artery for 1 h） control group, and ischemia/reperfusion with PPTA treatment group. In PPTA group, PPTA was injected via the femoral vein immediately after reperfusion, and ischemia/ reperfusion control group received saline injection. In 6 guinea pigs from each group, the cochlear tissues were removed after 24 h of reperfusion for examination of expressions of IL-1β and TNF-α mRNA by real-time PCR, and the rest animals were used for immunohistochemical detection of Fas protein. Results Compared with those of normal group and blank control group, the expressions of IL-1β and TNF-a mRNA increased significantly after cochlear ischemia/reperfusion （P〈0.001）, but were lowered significantly by PPTA （P〈0.001）. Positive expression of Fas protein expression was detected in the Corti organ, spiral ganglion and stria vascularis in ischemia/reperfusion control group with sigruficantly higher IOD values than those of the other 3 groups （P〈0.05）. The IOD value showed no significant difference between PPTA-treated group, normal control group, and blank control group （P〉0.05）. Conclusions PPTA can suppress the expression of Fas protein and IL-1β and TNF-α mRNAs in the cochlea of guinea pigs with cochlear ischemia/reperfusion. The protective effect of PPTA against cochlear ischemia/reperfusion is mediated probably by inhibition of inflammatory responses and cell apoptosis.

关 键 词：缺血再灌注 盐酸椒苯酮胺 白介素-1Β 肿瘤坏死因子-Α FAS蛋白 

分 类 号：R285.5[医药卫生—中药学]