热休克蛋白47在日本血吸虫病肝纤维化病程的动态变化  

Dynamic change of heat shock protein 47 in Schistosoma japonicum-induced hepatic fibrosis

作　　者：邓菊红[1] 陶然[2] 焦云桃[2] 李兰[2] 范翔雪[2] 黄加权[2] DENG Ju-hong TAO Ran JIAO Yun-tao LI Lan FAN Xiang-xue HUANG Jia-quan(Department of Internal Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Chin)

机构地区：[1]华中科技大学同济医学院附属梨园医院内科,武汉430077 [2]华中科技大学同济医学院附属同济医院感染科,武汉430030

出　　处：《传染病信息》2017年第3期156-160,167,共6页Infectious Disease Information

基　　金：湖北省血吸虫病防治项目基金(XF2010-15;XF2012-17);国家"十二五"科技重大专项(2014ZX10005001)

摘　　要：目的观察热休克蛋白47(heat shock protein 47,HSP47)在日本血吸虫病患者肝脏组织中的表达情况及其在日本血吸虫病肝纤维化小鼠动物模型中的动态变化。方法收集2008—2012年期间同济医院门诊和住院部日本血吸虫病肝纤维化患者肝穿标本72例。用免疫组织化学法检测HSP47表达;Masson染色观察胶原增生情况;实时荧光定量PCR检测HSP47、Ⅰ型胶原、结缔组织生长因子(connective tissue growth factor,CTGF)及转移生长因子-β1(transforming growth factor-β1,TGF-β1)m RNA水平的表达。构建实验性日本血吸虫病肝纤维化小鼠模型,分别于感染后第6、8、12周取小鼠肝组织,用免疫组织化学法检测HSP47表达,采用实时荧光定量PCR及Western blot检测HSP47的m RNA和蛋白水平表达及Ⅰ型胶原纤维增生情况。结果日本血吸虫病肝纤维化患者肝组织中的HSP47主要表达在肝脏间质细胞及虫卵结节周围,并随纤维化程度进展显著增多(P均<0.01),与Ⅰ型胶原增生趋势平行。各纤维化分期患者肝组织胶原及纤维化相关因子CTGF及TGF-β1 m RNA表达均明显高于S0期无纤维化患者(P均<0.01)。在肝纤维化模型小鼠中HSP47随纤维化进展其表达亦显著升高,感染后第6、8、12周,HSP47及Ⅰ型胶原的表达量均显著高于正常对照小鼠(P均<0.01),同血吸虫病肝纤维化患者的表达趋势一致。结论 HSP47在日本血吸虫病肝纤维化患者和日本血吸虫病动物模型肝组织中表达均上调,且随Ⅰ型胶原、CTGF、TGF-β1增多呈相同趋势,其有望成为肝纤维化新的诊断标志和治疗靶点。Objective To assess the expression of heat shock protein 47 （HSP47） from the liver tissues in patients with Schistosoma japonicum-induced liver fibrosis, and to observe the dynamic changes of HSP47 expression in a rodent model of Schistosoma japonicum-induced liver fibrosis. Methods Liver biopsy specimens from 72 outpatients and inpatients with Schistosoma japoniclun- induced liver fibrosis were collected from Tongji Hospital from 2008 to 2012. Immunohistochemical and Masson staining were performed to assess the expression of HSP47 and collagen proliferation, respectively. The mRNA expression levels of HSP47, collagen type I, connective tissue growth factor （CTGF） and transforming growth factor-β1 （TGF-β1） were measured by real-time PCR. Experimental inouse model of schistosomiasis liver fibrosis was established, liver tissue was harvested at the 6th, 8th, 12th week after infected, hnmunohistochemiswy was used to detect HSP47 expression. Real-time PCR and western blot analysis were performed to detect the expression of HSP47 and collagen type I at transcriptional and protein level. Results HSP47-positive cells of liver biopsy samples were mainly localized in interstitial areas and the periphery of egg granulomas. The number of HSP47-positive cells was significantly increased with the aggravation of liver fibrosis （P 〈 0.01）, in parallel with collagen type [ deposition. The relative expression levels of HSP47, collagen type I, CTGF and TGF-β1 mRNA were significantly increased from fibrosis stage 1 to stage 4, as compared to stage 0 （P 〈 0.01）. In rodent model of Schistosomajaponicum-induced hepatic fibrosis, the expression of HSP47 and collagen type I was significantly higher than that in normal control mice at the 6th week, the 8th week and the 12th week after they were infected （P 〈 0.01）, which was consistent with the expression change in patients with Schistosomajaponicum-induced liver fibrosis. Conclusions The expression of HSP47 is increased in patients with Schistosoma-induc

关 键 词：HSP47 肝纤维化 日本血吸虫病 Ⅰ型胶原 CTGF TGF-β1 

分 类 号：R512.91[医药卫生—内科学]