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去甲肾上腺素预处理对大鼠供心肌细胞凋亡及凋亡蛋白表达的影响

The protective effects of norepinephrine preconditioning on myocardial cell apoptosis and apoptosis related proteins in isolated rat heart
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摘要 目的 探讨去甲肾上腺素预处理是否可诱导心肌热休克蛋白70(HSP70)的合成,并进一步研究其对大鼠供心缺血再灌注后心肌细胞凋亡及凋亡蛋白表达的影响.方法 雄性Wistar大鼠18只,随机分为2组:对照组(n=9),腹腔注射生理盐水0.5 ml,24 h后取离体心脏灌注HTK心肌保护液,4℃保存3 h.然后行Langendorff离体心脏灌注,灌注Krebs-Henseleit(K-H)液2 h.实验组(n=9),腹腔注射重酒石酸去甲肾上腺素(溶于生理盐水中)3.1 μmol/kg(0.53 mg/kg),腹腔注射24 h后取离体心脏,处理方法同对照组.心脏灌流结束后取材测定各组心肌HSP70表达,TUNEL法测定心肌细胞凋亡率,免疫组化法测定凋亡蛋白Bcl-2、Bax的表达,并对相关指标做统计学处理比较.观察心肌细胞光镜结构和电镜下的超微结构.结果 实验组心肌组织HSP70表达明显高于[(17.78±1.82)%]对照组[(5.22±1.05)%],心肌细胞凋亡率明显低于[(5.57±1.05)%]对照组[(9.44±1.27)%],凋亡相关蛋白Bcl-2明显高于[(41.88±5.09)%]对照组[(31.36±3.27)%],Bax明显低于[(22.61±3.49)%]对照组[(40.52±4.17)%].实验组心肌组织光镜下结构以及电镜下超微结构的损伤较对照组明显减轻.结论 去甲肾上腺素预处理能诱导心肌组织HSP70高表达,HSP70对离体大鼠心脏经过缺血再灌注后具有明显的保护效应,去甲肾上腺素预处理能够明显保护心肌的结构和功能,抑制心肌细胞凋亡. Objective To investigate the synthesis of heat shock protein 70 (HSP70) induced by norepinephrine preconditioning on donor heart and its effects on myocardial cell apoptosis and apoptosis related proteins. Methods 18 Wistar rats were random divided into 2 groups, with 9 in each group. The rats in the control group were intraperitoneally injected with 0.5 ml saline. After 24 hours, hearts were isolated and stored with histidine-tryptophan-ketoglutarate (HTK) solution at 4 ℃ for 3 hours to establish Langendorff isolated heart models, and then isolated hearts were perfused by Langendorff model with Krebs-Hense leit (K-H) solution for 2 hours. The rats in the experimental group received intraperitoneally 3. 1 μmol/kg (0. 53 mg/kg) noradrenaline bitartrate that was dissolved in saline and hearts were isolated and stored after 24 hours. Followed process was the same as that in the control group. Myocardial HSP70, Bcl-2, Bax content, apoptosis index were measured, cell structures were observed under light and electron microscope.Results HSP70 in the experimental group were higher [(17.78 ± 1.82)%] than those in control group [(5.22 ± 1.05)%], and biochemical indicators in texperimental group[(41.88 ± 5.09)%, (22.61 ±3. 49 ) %] were better than those in control group [(31.36 ± 3. 27 ) %, ( 40. 52 ± 4. 1 7) %]. There were alleviated ultrastructure injures in experimental group compared with those in control group. Conclusions This study demonstrated that norepinephrine preconditioning could induce high expression of HSP70 and it could play a very important role during ischemia-reperfusion. It could protect the structure and function of myocytes in isolated rat hearts and inhibited myocardial apoptosis.
出处 《中国医师杂志》 CAS 2010年第4期462-465,共4页 Journal of Chinese Physician
关键词 去甲肾上腺素/药理学 肌细胞 心脏/药物作用 细胞凋亡 HSP70热休克蛋白质类/生物合成 基因 bcl-2/生物合成 bcl-2相关X蛋白质/生物合成 Norepinephrine/PD Myocytes, cardiac/DE Apoptosis HSP70 heat-shock proteins/BI Genes, bcl-2/BI Bcl-2-associated X protein/BI
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