摘要
目的探讨重组人胰岛素样生长因子-1（rhIGF-1）对大鼠急性缺血性坏死心肌的保护作用及其作用机制。方法6周龄sD大鼠，用异丙肾上腺素制成急性心肌缺血性坏死模型，随机分成模型组2d；模型组14d组；IGF-12d和IGF-114d组，另设正常组，每组8只。IGF-1组给予rhIGF-1 50μg·kg^-1·d^-1尾静脉注射，其他组给等量生理盐水。分别于2d和14d处死大鼠。放射免疫分析法测定大鼠血清和心肌组织IGF-1含量；TUNEL法检测大鼠心肌细胞凋亡并计算心肌细胞凋亡指数（AI）；免疫组化法测定心肌细胞的Bax蛋白；透射电镜观察心肌的超微结构。结果14d时模型组的血清和心肌IGF-1水平显著高于正常组（P〈0．05）；给药组体内IGF-I显著高于正常组和模型组（P〈0．05）。模型组的心肌细胞凋亡指数和Bax显著高于正常组和IGF-1组。透射电镜下可见，IGF-1组心肌细胞肿胀和损伤坏死明显减轻，尤其是IGF-1 14d组。结论静脉给予rhIGF-1可以有效地减轻心肌细胞的缺血和坏死，而IGF-1通过下调Bax蛋白后的抗心肌细胞凋亡作用可能是其重要的作用机制。
Objective To observe protective effects of reconstructed human insulin hke growht fator-1 （rhlGF-1） on ischemic necrosis myocardium in rats. Method Six-week old male Sprague-Dawley rats were made to estabhsh acute myocardial ischemia model by administration of isoprenalin, and then were divided into five groups, namely, 2-day model group, 14-day model group, 2-day IGF-1 group, 14 day IGF-1 group, and control group. Each group was consisted of 8 rats. The rats of both IGF- 1 groups received 50 μg/（kg·d） rhIGF- 1 intravenously via tail vein and the rats of other three groups were given saline insteas. The levels of IGF-1 in serum and myocardium were detected by using assay （IRA） and Bax in myocardium was measured by using immunohistochemistry inehtod. The myocardium apoptosis was evaluated by using terminal deoxynucleotidyl transferass-mediated dUTP and labehng （TUNEL） assay and the apoptofic index （AI） was expressed as a percentage of the number of apoptotic cells per total nuclei in each high-powered field （HPF）. The ultra-structures of myocardium was observed by transmission electron microscopy （TEM）. Results The levels of IGF-1 in myocardium and serum in the rats of 14-day model group were significantly higher than that those in the rats of control group, and rats of two IGF-1 groups had much higher concentrations of IGF-1 in myocardium and serum than those in both model group and control group （ P 〈 0.05）. Compared with the model rats, the rats of IGF-1 groups displayed great alleviation of the cells in ultrastruchture and especially the rats of 14-day IGF-1 group showed very similar characteristic of ultrastructure to those of normal rats. Conclusions IGF-1 has a protective effect against isehemic necrosis of myocardium, and injection of rhlGF-I can lessen effectively the isehemie necrosis of myocardium. The underlying mechanism of protective effects of IGF-1 against ischemic necrosis of myocardium may be attributed to the decrease in Bax down-regulated.
出处
《中华急诊医学杂志》
CAS
CSCD
2008年第2期173-176,共4页
Chinese Journal of Emergency Medicine
基金
安徽省教育厅自然科学研究项目基金资助（2004ki348）
