炎症因子TNF-α/IL-6对透析患者骨骼肌消耗及Myostatin和Atrogin-1表达的影响  

The effect of inflammatory cytokines TNF-α/IL-6 on muscle wasting and expressions of myostatin and atrogin-1 in hemodialysis patients

作　　者：丁婷婷[1,2] 王会玲 陆石 田军 胡伟锋 张金元 

机构地区：[1]解放军第四五五医院肾脏科,上海200052 [2]上海中医药大学 [3]南京军区肾脏病研究所,上海200052

出　　处：《中国血液净化》2013年第11期581-585,共5页Chinese Journal of Blood Purification

基　　金：上海启明星跟踪基金(No.07QH14020);上海浦江人才基金(10PJD016)~~

摘　　要：目的研究血液透析患者骨骼肌消耗状态与炎症因子水平及肌萎缩基因表达的关系。方法选择维持性血液透析(maintenance hemodialysis,MHD)患者42例(HD组),以30例健康人群为正常对照组(Ctl)。主观全面营养评价法(SGA)法评估患者营养状态,采集人体测量学数据,收集临床生化指标,Elisa方法检测C-反应蛋白(CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)等炎症因子水平;留取6位透析患者骨骼肌标本,与4位年龄性别匹配的非肾病者为对照,行HE染色并光镜下观察肌纤维形态,测量和分析肌纤维直径。荧光定量PCR检测肌萎缩标志分子Myostatin、Atrogin-1及炎症因子的转录水平。结果 HD组患者的体质量及体质量指数(BMI)低于健康对照组,其血尿素氮、肌酐和尿酸水平明显升高,并伴轻度贫血,其血清总蛋白和白蛋白、转铁蛋白等营养指标虽然在正常范围,但较对照组明显降低,血脂、血糖与对照组比较无差异;HD组的CRP、TNF-α和IL-6等炎症因子水平显著升高,P<0.05;骨骼肌标本光镜下观察到HD组肌纤维形态较纤细、萎缩,肌束间隙较宽,肌纤维直径降低;荧光定量PCR检测结果显示透析患者肌肉组织的myostatin mRNA转录水平上调5.96倍,Atrogin-1 mRNA上调2.43倍;同时TNF-α和IL-6mRNA转录水平分别上调8.37倍和3.36倍。结论血液透析患者骨骼肌消耗性营养不良与炎症因子水平升高相关;肌肉组织的TNF-α、IL-6表达上调,激活myostatin和Atrogin-1的转录,可能是引起骨骼肌消耗的重要机制。Objective To study the impact of inflammatory cytokines on muscle wasting and the expression of genes involving in muscle atrophy regulation in patients on maintenance hemodialysis （MHD）.Methods A total of 42 MHD patients were enrolled in this study （MHD group）,and 30 healthy adults with matched gender and age were used as the control group.Their biochemical and anthropometrical data were collected.Serum C-reactive protein （CRP）,interleukin-6 （IL-6） and tumor necrosis factor alpha （TNF-α）were measured by ELISA.Histology of muscle biopsies from 6 MHD patients and 4 non-MHD patients were examined after H-E staining by microscopy.The transcription levels of myostatin,atrogin-1,TNF-α,and IL-6 in muscle were measured by real-time PCR.Results Patients in MHD group had lower body weight and body mass index （BMI）,higher levels of serum BUN,cretinine and uric acid,slight anemia,lower plasma protein,albumin and pre-albumin but still in the lower ranges of normal limits,normal serum lipids and glucose,as ell as higher levels of serum CRP,TNF-α and IL-6 （P＜0.05）,as compared with those in control group.Microscopically,muscle samples showed slim and atrophic fibers with wide spaces between muscle fibers in MHD patients.Quantitative RT-PCR demonstrated that the mRNA levels of myostatin,atrogin-1,TNF-α and IL-6 increased by 5.96,2.43,8.37 and 3.36 times,respectively,as compared with those in control group.Conclusions Malnutritional muscle wasting in MHD patients may relate to the increase of inflammatory cytokine levels.Up-regulation of myostatin and atrogin-1 and activation of TNF-α and IL-6 transcription may be the important mechanisms underlying the muscle wasting in MHD patients.

关 键 词：透析 营养不良 骨骼肌消耗 炎症因子 

分 类 号：R318.16[医药卫生—生物医学工程]