Effects of insulin-like growth factor-1 gene transfer on myosin heavy chains in denervated rat laryngeal muscle
Effects of insulin-like growth factor-1 gene transfer on myosin heavy chains in denervated rat laryngeal muscle
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DOI：
10.1097/00005537-200402000-00035
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发表时间：
2004-02-01
期刊：
影响因子：
2.6
通讯作者：
O'Malley, BW
中科院分区：
文献类型：
--
作者：
Flint, PW;Nakagawa, H;O'Malley, BW
目的/假设：为了确定人胰岛素样生长因子-1的肌肉营养活性是否促进神经损伤后正常肌球蛋白重链组成的恢复，分析了人胰岛素样生长因子-1基因转移后失神经大鼠喉肌的肌球蛋白重链组成。研究设计：以动物模型研究基因转移对喉麻痹的影响。方法：麻醉大鼠左侧喉返神经和喉上神经切断后缝合。进行中线甲状腺切除术，并将含有肌肉特异性表达系统和hIGF-1DNA的聚乙烯基制剂注射到甲状旁肌(治疗组)或生理盐水(对照组)。30d后处死动物，取甲状旁肌进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)。通过密度测量来确定MHC的组成。结果：如前所述，失神经喉肌的MHC组成以IIB和IIL减少，ILA/IIX上调为特征。与对照组相比，hIGF-1处理组的IIB和IIL表达显著增加，IIA/X型表达显著降低。结论：hIGF-1基因治疗可使失神经肌肉MHC组成正常化，抑制IIA/X型MHC，促进III型MHC表达。
Objectives/Hypothesis: To determine whether the myotrophic activity of human insulin-like growth factor (hIGF)-1 promotes restoration of normal myosin heavy chain (MHC) composition after nerve injury, MHC composition was analyzed after hIGF-1 gene transfer in denervated rat laryngeal muscle. Study Design: Animal model to study effects of gene transfer on laryngeal paralysis. Methods: In anesthetized rats, the left recurrent and superior laryngeal nerves are cut and suture ligated. A midline thyrotomy is performed, and the thyroarytenoid muscle is injected with a polyvinyl-based formulation containing a muscle specific expression system and hIGF-1 DNA (treatment group) or saline (control group). After 30 days, animals were killed, and the thyroarytenoid muscle was removed and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric measurements were obtained to determine composition of MHCs. Results: As previously described, MHC composition in denervated laryngeal muscle was characterized by a decrease in type IIB and IIL, and up-regulation of ILA/IIX. Compared with controls, hIGF-1 treated animals demonstrated a significant increase in expression of type IIB and IIL and a significant decrease in expression of type IIA/X. Conclusions: These findings suggest that the myotrophic effect of hIGF-1 gene transfer results in normalization of MHC composition in denervated muscle, with suppression of type IIA/X MHC and promotion of type III, expression.