小型猪肝硬化模型肝脏病理及生化指标的变化

目的探讨小型猪肝硬化模型制备过程中肝脏病理学及生化指标的变化。方法选用同种系巴马小型猪50头,随机分为实验组40头,对照组10头,雌雄不限,4月龄,体重15-20kg。实验组予四氯化碳复合因素造模法喂养,正常组予饲料及清水喂养。于造模的0、4、8、12、16、20、24周末进行肝脏穿刺活检及耳缘静脉抽血进行数据采集,对比分析肝纤维化一肝硬化制模过程中的肝脏病理学及生化指标的变化。结果24周末,对照组获得数据S0期70例次;实验组获得数据轻度肝纤维化（S1＋S2期）82例次,重度肝纤维化（S3＋S4期）62例次,肝硬化共39例次。从正常组到肝硬化组丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、血清肌酐及球蛋白呈逐渐升高的趋势,而白蛋白,A／G比值呈逐渐下降的趋势,凝血酶原时间则逐渐延长,统计学分析,组间存在明显差异（P〈0．01）。结论四氯化碳复合因素造模法可以成功制备出小型猪肝硬化模型,肝纤维化不同阶段肝脏病理学和生化指标均发生明显变化。     

11种生化项目在肝脏疾病中的变化分析

肝脏疾病时体内存在多方面代谢紊乱 ,其中包括多种生化改变。为进一步探讨生化各项指标含量变化与肝病发生、发展和转归关系 ,我们观察包括总胆汁酸 (TBA)、 5′-核苷酸酶 (5′- NT)、胆碱酯酶 (CHE)、γ-谷氨酰胺转肽酶 (GGT)、碱性磷酸酶 (ALP)、丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、直接胆红素 (D- BIL)、总胆红素 (T- BIL )、白蛋白 (ALB)、球蛋白 (GIO)在内 1 1种生化项目在各类肝病中变化及其相互关系。现报告如下。1　资料与方法1 .1　研究对象　肝病组 2 5 8例 ,其中男性 1 5 3例 ,女性 1 0 5例 ,年龄…     

慢性乙型肝炎患者肠道菌群与肝脏生化指标的相关性

乙型肝炎病毒感染引起的慢性乙型肝炎(Chronic hepatitis B,CHB)是一种全球性流行疾病,严重时可引起肝功能衰竭,甚至发展成肝硬化和肝癌.也已发现CHB的发生和发展与肠道菌群的组成和结构的变化密切相关.为进一步探究肠道菌群结构与肝脏生化指标之间的联系,文中随机纳入14名CHB患者和11名健康对照者(Co...     

不同病理类型的原发性甲状旁腺功能亢进临床特征及生化指标的相关性分析

摘要 目的：分析不同病理类型的良性原发性甲状旁腺功能亢进（primary hyperparathyroidism,PHPT）患者临床特征和术前术后生化指标变化的不同,探讨其相关性,为该病的诊断与治疗提供思路。方法：收集行手术治疗的良性PHPT患者56 例,回顾性分析其临床资料及术前术后生化指标的变化,并按术后病理结果对其进行分组,比较其临床特征及生化指标的差异。结果：按病理类型将患者分为4组：甲状旁腺腺瘤（PA组）21 例（37.5%）,甲状旁腺腺瘤样增生（PAH组）28 例（50.0%）,甲状旁腺非典型腺瘤样增生（PAAH组）5例（8.93%）,甲状旁腺腺瘤合并甲状旁腺腺瘤样增生（PA+PAH组）2例（3.57%）。PHPT患者中女性明显高发,男女比例为1：5.22,且在PAH组所占比重明显高于PA组（P>0.05）。各组临床表现无明显差异。术前PTH在PAAH组明显高于PAH组,而术前血钙、血磷、25-羟基维生素D3在各组间比较无显著性差异。多处病灶有66.67%发生在PAH组,组间比较有显著性差异（x²=20.160a, P=0.000）。术后病理标本最大直径在PA组明显大于PAH组（P<0.05）,而在其余各组间比较无统计学差异（P>0.05）。PTH在术中标本切除后数值迅速下降,在术后第一天略有上升;血钙在术后呈持续下降趋势。PTH及血钙的下降幅度在各组间比较无显著性差异（P>0.05）。结论：良性原发性甲状旁腺功能亢进症中老年女性高发,尤其在PAH组明显高发。各种病理类型临床表现无差异。多处病灶主要集中在PAH组,PA组术后病理标本最大直径最大,PAAH组术前PTH水平最高,应对PAAH组患者加强术后PTH随访。     

纳米ZnO对斑马鱼肝脏生理生化指标的影响

研究了纳米ZnO对斑马鱼肝脏生理生化指标的影响。当斑马鱼暴露在ZnO纳米颗粒浓度为2.8 mg/L、5.6mg/L、11.2 mg/L、22.4 mg/L和44.8 mg/L时,分别测定了6 h、12 h、24 h、48 h和72 h时斑马鱼肝组织中的GSH、MDA、Na＋K＋-ATPase的含量和24 h ROS的变化,结果显示：与对照组相比,处理组中斑马鱼肝组织中GSH的含量显著减少（P〈0.05）,MDA含量随处理浓度的升高却显著增加（P〈0.05）,Na＋K＋-ATPase活性随暴露时间先显著降低后显著升高（P〈0.05）,24 h ROS含量高于对照组（P〈0.05）,说明斑马鱼肝组织的生理活动受到ZnO纳米颗粒的影响,且有时间和浓度依赖性。     

原发性胆汁性肝硬化家系成员的发病及机制初探

目的:研究原发性胆汁性肝硬化(PBC)家系患者发病时的临床表现、生化指标及人类白细胞抗原(HLA)基因分型的特征,分析该疾病的发病机制,以提高对该病的认识。方法:分别用临床生化分析试剂盒、间接免疫荧光法、免疫印迹法和微阵列聚合酶链式反应(PCR)等技术对收集的31个家系129例一级亲属进行生化指标、自身抗体和HLAⅡ基因分型的相关检测。结果:5个家系出现免疫异常,表现在抗核抗体(ANA)阳性,但仅有一个家系的一个成员出现抗线粒体抗体(AMA)M2型阳性,可诊断为PBC。其中,发现免疫异常的5个家系中2例一级亲属出现肝功能异常,两个家系发现HLAⅡ-DRB1(*08)基因型,另外两个家系共同存在HLAⅡ-DRB1(*07)基因型。结论:PBC具有一定的家族聚集性,其发病可能与HLAⅡ-DRB1(*08)密切相关。     

饲料中非蛋白能量源对草鱼血清生化指标和肝脏组织的影响

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熊去氧胆酸治疗原发性胆汁性肝硬化临床观察

目的探讨熊去氧胆酸治疗原发性胆汁性肝硬化的临床效果。方法选取某医院于2014年7月至2015年7月收治的原发性胆汁性肝硬化患者98例作为临床研究对象,随机将患者分为观察组和对照组,每组49例。两组患者均给予基础治疗,之后对照组患者采用通胆汤进行治疗,观察组患者在对照组的基础上加用熊去氧胆酸进行治疗。比较两组患者的治疗效果。结果根据分析结果,观察组患者的完全反应率明显高于对照组,并且肝功能指标明显优于对照组,比较结果具有显著差异性(P0.05)。结论熊去氧胆酸治疗原发性胆汁性肝硬化的临床效果良好,值得推广使用。     

贝飞达对原发性胆汁性肝硬化患者细胞因子的影响

目的探讨微生态调节剂对原发性胆汁性肝硬化（PBC）的影响。方法34例PBC患者为我院住院患者,均有肝功能异常,随机分为2组,一组为常规治疗组,给予糖皮质激素类、熊去氧胆酸及其他免疫抑制／增强剂药物治疗,另一组为贝飞达治疗组,在常规治疗基础上加用贝飞达。经过1个月的治疗,采血检测细胞因子及肝功能,对结果进行统计学处理。结果贝飞达治疗组同常规治疗组进行比较,在降低细胞因子水平改善肝功能方面差异有显著性。结论贝飞达通过调整肠道菌群,控制内毒素血症,可以调整原发性胆汁性肝硬化患者的免疫功能,改善肝功能。     

慢性乙肝肝硬化患者肝性脑病不同分级与肝脏储备功能的相关性

回顾性研究分析慢性乙肝肝硬化并发不同分级的肝性脑病（HE）患者的临床特点,探究影响HE患者预后的因素。

将380例HE患者根据临床症状进行分级,分为1～4级。分析各级HE患者的性别、年龄、实验室检查情况、终末期肝病模型（MELD）、谷草转氨酶与血小板计数比值（APRI）及白蛋白与总胆红素比值（ALBI）。采用Spearman相关性分析轻、重型HE的影响因素,并使用多因素Logistic回归法分析HE预后的影响因素,最后选用ROC曲线来评估各种独立变量对HE预后的预测价值。

1～4级HE患者组间性别、年龄差异均无统计学意义（均P＞0.05）,而血氨、MELD、APRI和ALB差异均有统计学差异（均P＜0.05）。轻、重型HE患者中性粒细胞计数和淋巴细胞计数的比值（NLR）、血氨、总胆红素（TBil）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、肿瘤坏死因子（TNF-α）、MELD、APRI及ALBI差异有统计学意义（均P＜0.05）。相关性分析显示,NLR、PLR、血氨、TBIL、ALT、AST及TNF-α是重型HE的独立影响因素。血氨及MELD评分与肝脏储备功能的相关性最高。NLR、血氨、TBil、TNF-α、高MELD评分及合并电解质紊乱均为HE预后的独立影响因素。ROC曲线分析显示,NLR的曲线下面积最大,其灵敏度最高、特异度也最大。

MELD、APRI和ALBI可用来评估不同分级HE患者的肝脏储备功能。在轻、重型HE中,血氨及MELD评分影响最大。在评估预后影响因素中,NLR水平可作为HE患者预后不良的危险因素。

     

Treatment of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects middle age women. Most patients are diagnosed when asymptomatic. The disease is characterised by chronic, granulomatous inflammation of the small bile ducts, which leads to progressive ductopenia, cholestasis, fibrosis, cirrhosis and eventual liver failure. All PBC patients with abnormal liver biochemistry should be considered for therapy. Ursodeoxycholic acid (URSO) treatment reduces intracellular hydrophobic bile acid levels and thereby may have a cytoprotective effect on cell membranes. URSO may also act as an immunomodulating agent. Multicenter randomised controlled trials proved that the treatment is associated with a marked improvement in serum biochemical markers of cholestasis, i.e. bilirubin, ALP, GGT, including fall in serum cholesterol levels. Treatment does not seem to benefit the symptoms of fatigue, pruritus, and osteoporosis. UDCA has been shown when given in a dose of 15 mg/kg daily for up to 4 years to prolong the time to liver transplantation or death. Immunosuppressive therapy: based on the immunological abnormalities, several immunosuppressive drugs have been tested. Neither azathioprine nor cyclosporine was found in large enough trials to show beneficial effect on survival. D-penicillamine, cholchicin, methotrexát, prednisolone were found without significant long-term benefit. Combination therapy with URSO and budenoside appears to add some benefit to URSO monotherapy, but further studies are needed. Liver transplantation. The most crucial question is the timing. Serum bilirubin, Mayo risk score and some other factors such as uncontrollable pruritus and severe osteoporosis influence the decision. Recurrence of PBC in allograft is rare, the progress is slow, and is no reason for not recommending transplantation. Symptomatic treatment of pruritus, sicca syndrome and preventive treatment of osteoporosis, neuropathy and fat soluble vitamin deficiency is also important.     

New insights to the immunopathology and autoimmune responses in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune liver disease with profound changes in different compartments of the immune system, including those involved in innate, and adaptive immunity. New data from epidemiological studies of PBC have reinforced the thesis that the cause for this relatively uncommon disease is likely to be a combination of both environmental factors and a susceptible genetic predisposition. Recent findings of abnormalities of the innate immune system in PBC suggest that they may serve as links between the environmental factors and the early events in PBC development. Viral and bacterial infections as well as xenobiotics are some of the potential environmental factors that have been implicated in this complex process. Identification of the etiological factors for PBC will point to new preventive or therapeutic treatments.     

Mitochondria and autoimmunity in primary biliary cirrhosis

Primary biliary cirrhosis is an enigmatic autoimmune liver disease that predominantly affects women and is characterized by antimitochondrial antibodies and specific destruction of small bile ducts. Interestingly, patients with this disease not only have high titer antibodies to mitochondria, but also highly directed, liver-specific CD4 and CD8 cells directed at the same mitochondrial autoantigens. These mitochondrial autoantigens are all members of the 2-oxo dehydrogenase complex family and include the E2 component of pyruvate dehydrogenase as the major autoantigen. Moreover, the epitopes recognized by CD4, CD8 T cells and autoantibody, are all directed within the same region, namely the lipoyl domain of pyruvate dehydrogenase complex-E2. All cells in the body have mitochondria but there appear to be specific destruction of biliary cells. We believe that this specific destruction is secondary to a highly directed mucosal response that focuses on biliary cells because of the involvement of a polymeric immunoglobulin receptor, the presence of immunoglobulin A in mucosal secretions, and the unique apoptotic properties of biliary epithelium.     

Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis

Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2(163-176). We studied the ability of eight T cell clones (TCC) specific for PDC-E2(163-176) to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2(163-176), an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDC-E2(34-47)), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2(163-176), E. coli OGDC-E2(34-47)) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation-dependent responses to OGDC-E2 become anergic to PDC-E2 when preincubated with mimic, even if costimulation is independent for PDC-E2(163-176). Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2(163-176)-pulsed L-DR53 but became anergic using L-DR53 pulsed with PDC-E2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBC-specific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen may restore rather than break peripheral tolerance.     

The autoimmunity of primary biliary cirrhosis and the clonal selection theory

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease in which an immune-mediated injury targets the small intrahepatic bile ducts. PBC is further characterized by highly specific serum antimitochondrial autoantibodies (AMAs) and autoreactive T cells, a striking female predominance, a strong genetic susceptibility and a plethora of candidate environmental factors to trigger the disease onset. For these reasons, PBC appears ideal to represent the developments of the clonal selection theory over the past decades. First, a sufficiently potent autoimmunogenic stimulus in PBC would require the coexistence of numerous pre-existing conditions (mostly genetic, as recently illustrated by genome-wide association studies and animal models) to perpetuate the destruction of the biliary epithelium by the immune system via the persistence of forbidden clones. Second, the proposed modifications of mitochondrial autoantigens caused by infectious agents and/or xenobiotics well illustrate the possibility that peculiar changes in the antigen structure and flexibility may contribute to tolerance breakdown. Third, the unique apoptotic features shown for cholangiocytes are the ideal setting for the development of mitochondrial autoantigen presentation to the immune system through macrophages and AMA; thus, turning the non-traditional mitochondrial antigen into a traditional one. This article will review the current knowledge on PBC etiology and pathogenesis in light of the clonal selection theory developments.     

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

Autoantibodies in the sera of patients with primary biliary cirrhosis, shown previously to recognise the E2 polypeptide of the mammalian pyruvate dehydrogenase complex (PDC), have been demonstrated to react with the E2 component of PDC from bacteria (E. coli) and yeast (S. cerevisiae). Limited tryptic digestion, which cleaves E2 into well-characterised domains, followed by Western blotting indicates that the main immunodominant region of PDC E2 lies within the lipoic acid-containing domains of the polypeptide.     

肝硬化合并结核病患者的临床特征

目的 分析肝硬化合并结核病患者的临床特征,为该类患者的治疗提供参考。 方法 回顾性分析2014年9月至2017年7月于浙江大学医学院附属第一医院住院的肝硬化合并结核病患者的相关资料,总结患者的临床特征。 结果 共收治68例肝硬化合并结核病患者,其中男性50例(73.5%),女性18例(26.5%),平均年龄(59.9±13.7)岁。在所有患者中,肝硬化最常见的原因是HBV感染(46例,67.7%)和酒精(9例,13.2%)。肺结核(43例)、结核性腹膜炎(13例)、结核性胸膜炎(12例)是最常见的结核类型,此外骨关节结核、结核性脑膜炎、结核性心包炎、泌尿系结核、肠结核、淋巴结结核均可见。该类患者常见临床表现为乏力、腹胀,出现发热的患者不足半数,有盗汗表现的更为罕见。 结论 肝硬化患者并发结核后可使病情复杂化,增加治疗难度。此外部分患者临床表现不典型,需提高警惕,避免漏诊。     

老年肝硬化并发自发性腹膜炎临床特点及病原学分析

目的探讨老年肝硬化并发自发性腹膜炎(SBP)患者的临床特点及腹水病原菌分布及其耐药情况,指导临床合理用药。方法回顾性分析老年肝硬化并发SBP患者的临床特点,并对118例腹水病原菌培养结果阳性的120株病原菌进行鉴定和耐药分析。结果365例SPB患者治愈113例(31.0%),好转99例(27.1%),病情恶化自动出院及死亡153例(41.9%)。发病隐匿164例(44.9%),急性发病201例(55.1%)。365例SBP患者腹水病原菌培养阳性118例(32.3%),共分离出病原菌120株,其中大肠埃希菌检出率最高,占40.0%(48/120),其次为肺炎克雷伯菌,占12.5%(15/120)。分离菌株的耐药情况比较严重,特别是大肠埃希菌对多种抗菌药物的耐药率60%。结论老年肝硬化并发SBP患者病情复杂,病死率高,且细菌耐药比较严重,应尽早进行腹水培养,依据药物敏感试验结果合理选用抗菌药物。     

Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis.

Previous studies suggested endotoxin, derived from the intestine through the portal blood to the liver, was predominantly metabolized by Kupffer cells. In the present study, fluorescent-labeled endotoxin injected into the rat portal vein was demonstrated not only in Kupffer cells but also in hepatocytes. Furthermore a great amount of labeled endotoxin was recovered in bile. In the livers of patients with primary biliary cirrhosis (PBC), immunohistochemistry demonstrated significant retention of endotoxin in the biliary epithelial cells, and treatment with ursodeoxycholic acid significantly reduced the retention in those cells. The study for detection of apoptosis demonstrated increased rates of apoptosis in hepatocytes and biliary epithelial cells in PBC liver, and the rate of apoptosis in biliary epithelial cells was significantly reduced after treatment with ursodeoxycholic acid. Immunohistochemistry in PBC liver demonstrated significant reduction of fluorescence intensity for a 7H6 antigen in biliary epithelial cells, indicating the increased paracellular permeability of bile ducts, because cellular immunolocalization of that antigen has been shown to be inversely correlated with the paracellular permeability of the tight junction. These results suggest that, in biliary epithelial cells, retention of endotoxin, increased apoptosis, and increased permeability of tight junctions may be involved in the pathogenesis of PBC.