华支睾吸虫致胆管癌发生发展的研究进展

华支睾吸虫是一种食源性寄生虫,其感染可导致宿主肝胆管病变,甚至诱发胆管癌。本文结合近年来的相关研究,从虫体的毒性作用、宿主的异常免疫反应以及其他病原体共感染等方面对华支睾吸虫导致胆管癌发生发展的致病机制进行阐述。     

肝吸虫引发胆管细胞癌发病机制的研究进展

肝吸虫病是一种危害性极大的食源性寄生虫病.全世界感染肝吸虫的人数大约有3500万,约有11亿人存在感染风险.长期肝吸虫感染引起最严重的并发症是胆管细胞癌(CCA),世界卫生组织国际癌症研究署已经将肝吸虫列为CCA的Ⅰ类致癌性病原体.近年来,有许多学者对肝吸虫感染的致癌机制做了相应的临床及实验研究,但至今其致癌机制尚未明...     

细胞凋亡在肝吸虫感染大鼠及肝吸虫病患者肝损伤的作用

目的 分析肝吸虫感染大鼠和肝吸虫病患者肝组织的病理改变及损伤情况,探讨细胞凋亡在肝吸虫感染所致肝损伤中的作用.方法 将Wistar大鼠分为2组:感染组60只,对照组20只.感染组大鼠经口饲感染囊蚴法建立肝吸虫感染模型,对照组大鼠采用生理盐水灌胃.于感染后第4、6、8、12周时处死动物.同时收集尸检获得的肝吸虫病患者及健康对照人体肝组织标本各4例.光镜下观察大鼠和人体肝吸虫感染情况以及肝组织的病理学改变;并用TUNEL法检测肝细胞的凋亡率.结果 光镜下各时间点感染组大鼠和肝吸虫病患者胆管壁增厚,胆管黏膜呈乳头状和腺瘤样增生,管腔内可见虫体及虫卵,胆管周围可见炎细胞浸润和少量纤维组织增生,汇管区周围有一些肝细胞出现核固缩,呈现细胞凋亡的形态特征.感染组大鼠第4、6、8、12周时肝细胞凋亡率分别为(7.15±1.50)%、(11.61±3.09)%、(13.21±3.47)%、(11.26±4.06)%,均明显高于对照组[(2.57±0.72)%、(3.17±0.77)%、(3.67±0.96)%、(2.84±0.87)%,t值分别为4.45、5.49、5.95、4.74,P均<0.01].肝吸虫病患者肝组织细胞凋亡率为(12.02±1.78)%,明显高于对照组[(2.03±0.68)%,t=15.13,P<0.01].结论 肝吸虫感染可以引起宿主肝细胞凋亡,后者可能与感染者肝损伤有关.

Abstract：

Objective To investigate the liver injury and pathological changes of rat and patients with Clonorchis sinensis(C, sinensis) infection, and to clarify the role of apoptosis in the injury induced by C. sinensis.Methods Wistar rats were divided into two group: 60 in infection group and 20 in control. The rats in infection group were infected with C. sinensis via oral feeding encysted cercaria;rats in control group were fed with normal saline. The rats were sacrificed 4, 6, 8 and 12 weeks after infection, respectively. Liver tissue specimens of the patients infected with C. sinensis were collected. The pathological changes of liver tissue were observed by light microscopy and the apoptofic rate of hepatocyte was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) assay. Results Parasites and eggs could he seen around the bile duct, and the duct was associated with mucosa and adenoma papillary hyperplasia, wall thickening, inflammatory cell infiltration, a small amount of fibrous tissue hyperplasia, and periportal liver cells surrounded by a number of nuclear condensation, all these changes meant morphological characteristics of apoptosis. Apoptotic rates of liver cells in infection group 4, 6,8 and 12 weeks after infection were (7.15 ± 1.50)%,(11.61 ± 3.09)%,(13.21 ± 3.47)% and (11.26 ± 4.06)%,respectively, which was significantly higher than that in control group [(2.57 ± 0.72)%, (3.17 + 0.77)%, (3.67 ±0.96)% and (2.84 ± 0.87)%, t values were 4.45, 5.49, 5.95 and 4.74, respectively, all P < 0.01]. Conclusions These findings indicate that C, sinensis can stimulate both hepatoeytic apoptosis and degeneration which may he related to clinical manifestations and liver lesions in patients with clonorchiasis.     

肝吸虫感染大鼠模型的建立及肝损伤的观察

目的 观察不同剂量的肝吸虫囊蚴感染大鼠后粪便中虫卵检出率及肝组织的病理变化.方法 分离采自疫区麦穗鱼体内的囊蚴,分别以25、50、100和200个囊蚴经口感染四组大鼠,同时设生理盐水灌注对照组.生理盐水涂片法检查大鼠粪便中虫卵,虫卵检出率达100％时宰杀动物,取肝脏制备组织切片.结果 成功建立了肝吸虫感染Wistar大鼠的实验动物模型,观察到肝吸虫感染大鼠和肝吸虫病患者肝组织有典型的肝胆管病理学改变.感染组大鼠感染后3w粪便虫卵检出率为70.8％;感染后4w为85.4％;感染后5w为93.8％;感染后6w检出率为100％.感染25个囊蚴组虫体回收率为17.3％;感染50个囊蚴组虫体回收率为15.7％;感染100个囊蚴组虫体回收率为42.8％;感染200个囊蚴组虫体回收率为31.7％.对照组均未检出虫卵及成虫.结论 感染后6w肝吸虫虫卵的检出率达高峰;感染100个囊蚴组虫体回收率最高.肝吸虫感染可以引起宿主肝细胞变性和坏死,是患者的临床表现及肝损伤的病理基础.     

华支睾吸虫致胆管癌的研究进展

华支睾吸虫是胆管癌的一个重要的生物性致癌因素,其成虫寄生在宿主的肝胆管内,成虫的机械性刺激、分泌排泄产物的化学刺激和成虫定居所致的慢性炎症等导致了寄生部位胆管的增生、癌变.该文从流行病学、动物实验及分子机制等方面对华支睾吸虫致胆管癌的研究进行了综述.     

蠕虫及肠道原虫感染与肠道菌群关系研究进展

肠道菌群是人体最大最复杂的生态系统,与肠道病毒和寄生虫等共同栖息在人或动物肠道内。已有研究表明,肠道菌群紊乱与多种疾病的发生、发展及预后密切相关。定植在宿主体内的寄生虫可直接或间接影响肠道菌群及其与机体的相对稳态,而肠道菌群结构及多样性的改变也会影响寄生虫感染及疾病的发生、发展和预后。本文就蠕虫及肠道原虫与肠道菌群相互关系研究进展作一综述。     

绦虫排泄分泌物与宿主免疫效应的相关研究进展

绦虫是常见的人兽共感染寄生虫。绦虫排泄分泌物(ESP)是绦虫在感染过程中分泌/排泄并直接暴露于宿主免疫系统的产物,是最可能引起宿主免疫效应变化的原因之一。近年来大量研究显示,该物质可诱导和调控宿主的免疫应答,与绦虫感染密切相关。绦虫ESP可诱导宿主产生正向免疫效应来控制感染,亦可诱导宿主产生负向免疫效应,从而逃避宿主的免疫攻击,建立长期感染。本文对绦虫ESP与宿主免疫效应的相关研究作一简要综述。     

胆汁酸、肠道微生物与胆管癌发生和发展关系的研究进展

胆管癌是一种起源于胆管上皮的恶性肿瘤,因发病隐匿,缺乏有效的早期诊断方法,一经发现均属于晚期,预后不良。胆汁酸是胆汁的主要成分,它可通过胆汁酸受体作用于胆管细胞,在胆管癌的发生演变中起着关键作用,而肠道微生物可通过调节胆汁酸代谢参与胆管癌的发生。现主要针对胆汁酸、胆汁酸受体在胆管癌发生和发展中的作用以及肠道微生物在其中...     

肠道菌群对结直肠癌发生及其诊治作用的研究进展

结直肠癌是人类目前常见的癌症之一,是全球癌症相关死亡的第二大原因。肠道菌群在维持肠道正常生理环境方面发挥重要作用,包括能量代谢、与正常肠道屏障系统相互作用、促进上皮细胞存活等。随着研究的不断深入,越来越多的研究表明,肠道菌群在结直肠癌发生、发展中发挥重要作用。目前普遍认为,肠道菌群诱导的结直肠癌作用机制与细菌产生的毒素释放增强诱导DNA损伤、肠道有益菌衍生代谢物减少、肠道上皮屏障功能障碍或肠道菌群生态失调等因素有关。     

人体蠕虫感染对肠道菌群影响的研究进展

人体蠕虫与肠道菌群相互作用,会直接或间接地影响人体健康。本文重点就旋毛形线虫、毛首鞭形线虫、似蚓蛔线虫、钩虫、缩小膜壳绦虫、华支睾吸虫、血吸虫等主要蠕虫与肠道菌群之间关系的研究进行综述,以期为相关疾病的诊断、治疗和预防等提供新的研究思路。     

Cellular responses during liver fluke infection in sheep and its evasion by the parasite

The cellular immune response in sheep to an acute and chronic primary and an acute secondary liver fluke infection were examined by immunohistology of liver tissue and flowcytometry of lymphocytes from the draining hepatic lymph nodes. Ten days after primary infection, portal tract areas surrounding migratory tunnels were infiltrated with CD4⁺ and CD8⁺ lymphocytes with fewer B cells and T19⁺ T cells. Micro abscesses were distributed sporadically in the liver parenchyma and young flukes could be easily observed in the liver tissue free from inflammatory cells. More intensive infiltration of the portal tract areas was observed during a secondary liver fluke infection characterized by a pronounced increase in eosinophils, B cells and CD4⁺ T cells. In addition, there was an increase in MHC class II⁺ fibroblastic-like cells surrounding the migratory tracts. In contrast to the primary infection, no young flukes were observed in the same tissue areas during the secondary infection. Chronic primary infections were characterized by perilobular fibrosis and a predominance of CD8⁺ and γδ-TCR⁺ T19^- T cells distributed within fibrotic strands. Distinct B cell follicles were observed in the fibrotic strands and near major bile ducts and necrotic patches. Pronounced lymphocyte infiltration could occasionally be observed surrounding liver fluke eggs lodged in liver tissue. A progressive increase in lymph node weight, cell number and CD4/CD8 ratio was observed in the acute and chronic primary infections. The role of the infiltrating cell populations and possible mechanisms of immune evasion by the parasite are discussed.     

三种吸虫感染与胆管癌发病关系的研究进展

由华支睾吸虫(Clonorchis sinensis)、麝猫后睾吸虫(Opisthorchis viverrini)和猫后睾吸虫(Opisthorchis fe-lineus)所引起的吸虫病是严重危害人类健康的食源性寄生虫病,在亚洲地区流行较为广泛,人们通过食含有囊蚴的生鱼或虾类而感染。长期且重度感染会造成肝脏机能障碍,如胆结石和胆囊炎等。近年来,越来越多的研究表明这三种吸虫与胆管癌之间存在着病因学联系。本文对他们之间的关系及胆管癌可能的发病机制进行综述。     

免疫性肝损伤相关细胞因子研究进展

乙型肝炎病毒等多种诱因导致免疫性肝损伤,促成肝细胞的病变的重要因素是免疫应答中产生的细胞因子。本文综述了有关细胞因子与免疫性肝损伤发病机制的实验研究进展。     

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats

BACKGROUND:Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress,hepatocellular injury and fibrosis.Quercetin is a flavonoid with antifibrotic,and hepatoprotective properties.However,the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood.The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model.METHODS:We divided male Wistar rats into 4 groups (n=8 for each):sham,sham+quercetin (30 mg/kg per day),BDL,and BDL+quercetin (30 mg/kg per day).Four weeks later,the rats were sacrificed,the blood was collected for liver enzyme measurements and liver for the measurement of Racl,Racl-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting,respectively.RESULTS:Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes.Furthermore,the mRNA and protein expression of Racl,Racl-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P＜0.05);quercetin treatment reversed these variables back toward normal (P＜0.05).Another interesting finding was that the antioxidant markers e.g.superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P＜0.05).CONCLUSION:Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue,while preventing the production of Racl,Racl-GTP and NOX1 proteins.     

植物提取物防治抗结核药致肝损害的研究进展

抗结核药物引起的肝损害已成为药物性肝炎最常见的因为之一,是结核患者停止化疗的主要因为.因此,减少抗结核药物所致的肝损害已成为结核化疗成败的关键因素.本文总结了目前国内外植物有效成分防治抗结核药致肝损害的研究情况,希望有助于该类药物在临床应用.     

中药和西药致急性药物性肝损伤临床和肝组织病理学特征对比分析

目的比较中药和西药致急性药物性肝损伤(ADILI)的临床特点和肝组织病理学改变。方法回顾性分析中药致ADILI患者96例和西药致ADILI患者113例,比较两类药物致ADILI的临床表现、生化学指标、免疫学指标及肝组织病理学改变的异同。结果两组患者临床表现和生化学指标相似,但中药组患者血清自身抗体阳性率为27.1%,显著高于西药组(14.2%,P<0.05);中药组肝组织点状或灶状坏死(93.8%)与西药组(94.7%)表现相似,但中药组中融合性坏死(51.0%)、界面炎(65.6%)和纤维间隔形成(54.2%)显著高于西药组(33.6%、50.4%和37.2%,P<0.05),且汇管区淋巴细胞-浆细胞浸润(26.0%)较西药组(19.5%,P>0.05)显著。结论中药和西药致ADILI的临床表现与生化学指标与西药所致者相似,但前者自身免疫反应和病理学改变更趋于严重。