Duchenne型肌营养不良患儿抗肌萎缩蛋白-糖蛋白复合物的表达及临床意义

Expression and clinical significance of dystrophin-glycoprotein complex in children with Duchenne muscular dystrophy

摘要:

目的 检测Duchenne型肌营养不良（DMD）患儿抗肌萎缩蛋白-糖蛋白复合物（DGC）的表达水平，并分析其临床意义。方法 收集2015年1月—2019年8月西安市儿童医院56例DMD患儿的临床资料并进行回顾性分析，记为DMD组；另回顾性分析同期该院52例经病理检查证实未患DMD小儿的临床资料，记为对照组。采用免疫荧光染色法检测腓肠肌组织中DGC的表达水平，DGC包括肌营养不良蛋白聚糖（α-DG、β-DG）、肌聚糖蛋白（α-SG、β-SG、γ-SG、δ-SG）、互生蛋白（Syntrophin）。比较两组DGC表达水平的差异；比较DMD组不同病情分级患儿DGC表达水平及缺乏程度的差异；分析DMD组抗肌萎缩蛋白（Dystrophin）与DGC表达的相关性。结果 DMD组和对照组Dystrophin、DGC表达的积分光密度（IOD）比较，差异有统计学意义（P <0.05），DMD组低于对照组。DMD组不同病情分级患儿Dystrophin、DGC表达的IOD值、缺乏程度分级比较，差异有统计学意义（P <0.05），且每两个亚组比较，差异有统计学意义（P <0.05），其中病情分级< 3级患儿Dystrophin、DGC表达的IOD值、缺乏程度分级均高于3～5级、>5级患儿（P <0.05），3～5级患儿Dystrophin、DGC表达的IOD值、缺乏程度分级均高于> 5级患儿（P <0.05）。免疫荧光染色结果显示，DGC阳性表达肌细胞膜上，可见薄且连续的、完整的环形荧光。DMD患儿Dystrophin染色与α-DG、β-DG、α-SG、β-SG、γ-SG、δ-SG及Syntrophin蛋白表达呈正相关（r =0.712、0.756、0.782、0.714、0.796、0.743和0.785，均P <0.05）。结论 DMD患儿DGC表达水平偏低，且均与Dystrophin染色有关，病情越严重，DGC表达水平越低。

Abstract:

Objective To detect the expressions of dystrophin glycoprotein (DGC) complex related proteins in Duchenne muscular dystrophy (DMD) and to analyze its significance.Methods The clinical data of 56 children with DMD and the clinical data of 52 children without DMD confirmed by gastrocnemius pathology were reviewed. Immunofluorescence staining was used to detect the expressions of Dystrophin and DGC complex related proteins in gastrocnemius, including dystrophin proteoglycan (α- DG and β- DG), myoglycan proteins (α- SG, β- SG, γ- SG, δ- SG), and syntrophin, and the differences between the two groups were compared. The the expressions of DGC complex related protein and the degrees of deficiency were compared among the different conditions in DMD group. The correlations between dystrophin staining and DGC complex related protein expressions in DMD group were analyzed.Results Compared with the integral optical density (IOD) values of α- DG, β- DG, α- SG, β- SG, γ- SG, δ- SG, and syntrophin expressions between the DMD group and the control group, there were statistically significant differences by t test (P < 0.05), which in the DMD group were lower than those in the control group. Compared with the IOD values and deficiency degrees of dystrophin and DGC complex related proteins among children with different conditions in DMD group, there were statistically significant differences by variance analysis (P < 0.05), and compared between each two subgroups, there were statistically significant differences by SNK-q test (P < 0.05), which in the grade 3 were higher than those in the grade 3 to 5 and grade 5, which in the grade 3 to 5 were higher than those in the grade 5. The Dystrophin expression was positively related to the expressions of α- DG (r = 0.712, P = 0.005), β - DG (r = 0.756, P = 0.001), α- SG (r = 0.782, P = 0.003), β- SG (r = 0.714, P = 0.012), γ- SG (r = 0.796, P = 0.000), δ- SG (r = 0.743, P = 0.008). and syntrophin (r = 0.785, P = 0.009) in DMD group.Conclusion The expressions of DGC complex related proteins in DMD of children are low, including α - DG, β- DG, α- SG, β- SG, γ- SG, δ- SG, and syntrophin proteins, which are related to the Dystrophin expression. The more serious the disease is, the lower the expressions of these proteins.