CAJ | 학술논문

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。
목적：탐토돈서이와백개소-1β（IL-1β）、종류배사인자-α（TNF-α）mRNA、Fas단백표체여이와결혈재관주손상관계급염산초분동알（PPTA）대돈서이와결혈재관주손상보호궤제。방법돈서64지수궤분위4조，매조16지，분별위정상조、공백대조조、결혈재관주대조조화결혈재관주PPTA조，매조수궤선6지용우RT-PCR검측，잉여10지용우면역조화。미혈관협협폐쌍측추동맥급우측경총동맥1 h송개동맥협이제조이와결혈모형，결혈재관주PPTA조우결혈1 h재관주후립즉경고정맥주사PPTA （10 mg/kg），결혈재관주대조조주사등량생리염수，24 h후취표본。용RT-PCR법검측IL-1β화TNF-α적mRNA적표체。결과결혈재관주대조조이와조직IL-1β、TNF-αmRNA표체량현저고우정상조화공백대조조（P<0.001）；결혈재관주PPTA조이와조직IL-1βmRNA、TNF-αmRNA표체량현저저우결혈재관주대조조（P<0.001）；결혈재관주조Corti기、라선신경절화혈관문Fas표체양성，적분광밀도치（IOD）치교기타삼조명현증고（P<0.05），결혈재관주PPTA간예조IOD치여정상조급공백대조조차이무통계학의의（P>0.05）。결론 PPTA가억제결혈재관주이와각부위IL-1β、TNF-αmRNA、Fas단백표체；PPTA가능통과억제염성반응급억제세포조망실현대이와결혈재관주손상적길항작용。
Objective To investigate the relationship between IL-1βand TNF-αmRNA 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-1βand TNF-αmRNAs 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.