南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (11): 1669-.

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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

李永贺，吴剑，李威，陈浩，万良财   

  • 出版日期:2013-11-20 发布日期:2013-11-20

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

  • Online:2013-11-20 Published:2013-11-20

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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-α mRNA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-1β mRNA、TNF-α mRNA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-α mRNA、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。

Abstract: 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-α 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 significantly 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.