SCN4A Met1592Val突变所致的永久性肌病体外成肌过程观察及碱性成纤维细胞生长因子的作用(英文)

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目的正常血钾性周期麻痹是由位于17号染色体上编码人类骨骼肌钠通道基因(SCN4A)发生突变所致,以肢体无力短暂、反复发作并完全恢复为特点,部分患者可发展为永久性肌病(permanent myopathy,PM),该病的发病机制尚不清楚,至今也无有效的治疗方法。本文观察SCN4A Met1592Val突变所致PM患者骨骼肌细胞体外生长过程,同时探讨外源性碱性成纤维细胞生长因子(basic fibro blast growth factor,bFGF)对PM防治作用的可能性。方法对两名来自一个由基因诊断确诊为SCN4A Met1592Val突变家系的患者和四名正常对照者的腓肠肌细胞进行体外培养,观察其生长过程;同时给予6个浓度(10ng/mL,20ng/mL,40ng/mL,80ng/mL,120ng/mL和160ng/mL)的bFGF刺激,用MTT法、考马斯亮蓝比色法、反复冻融细胞,对骨骼肌细胞增殖进行检测。结果腓肠肌细胞可体外培养,与在体发生过程相似,但PM组肌细胞发育迟滞;bFGF对肌细胞生长的增殖作用、促LDH、CK活性及蛋白质合成作用呈明显的浓度依赖性,浓度为120ng/mL时作用最显著(P<0.05),此时浓度再增大其效应反而下降,在浓度为160ng/mL时的作用大于80ng/mL,但无统计学意义(P>0.05)。结论PM患者受损腓肠肌在体外有再生能力,但融合成肌管能力极弱,存在再生障碍,不能对变性、坏死的肌纤维形成有效再生,故呈进行性肌纤维耗竭;外源性bFGF可促进PM患者体外培养骨骼肌细胞增殖分裂,并可促进肌管成熟,对进展性肌病应具有防治作用。 Objective Normal hyperkalemic periodic paralysis is caused by a mutation in the human skeletal muscle sodium channel gene (SCN4A) located on chromosome 17 characterized by transient, recurrent and complete recovery of limb weakness, and some patients develop permanent muscle The pathogenesis of this disease is not yet clear, so far there is no effective treatment. This study was to investigate the in vitro growth of skeletal muscle cells in patients with PM induced by SCN4A Met1592Val mutation and to explore the possibility of using basic fibroblast growth factor (bFGF) to prevent and treat PM. Methods Two gastrocnemius cells from a pedigree diagnosed as genetically diagnosed as SCN4A Met1592Val and four normal controls were cultured in vitro and the growth of the gastrocnemius cells was observed. Six different concentrations of 10ng / mL, 20ng / mL, 40ng / mL, 80ng / mL, 120ng / mL and 160ng / mL). The proliferation of skeletal muscle cells was detected by MTT assay and Coomassie blue assay. Results The gastrocnemius muscle cells could be cultured in vitro, which was similar to that in vivo, but the myocyte retardation in PM group was delayed. The proliferative effect of bFGF on myocyte growth and the activity of LDH and CK and the protein synthesis were in a concentration-dependent manner with a concentration of 120ng / mL (P <0.05). At this time, the effect was even more serious at a concentration of 160 ng / mL, but the effect was greater than 80 ng / mL, but there was no statistical significance (P> 0.05). Conclusions The gastrocnemius muscle in PM patients has regenerative ability in vitro, but the ability to fuse myoblasts is extremely weak, and there is aplastic dysfunction, which can not regenerate the degenerative and necrotic muscle fibers effectively. Therefore, the exogenous bFGF promotes PM Patients cultured in vitro proliferation and division of skeletal muscle cells, and can promote myotube maturation, should have a preventive effect on progressive myopathy.
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