丹芍化纤胶囊对肝纤维化大鼠PDGFR-β和p-ERK1/2的影响

目的通过观察丹芍化纤胶囊对肝纤维化大鼠PDGFR-β和p-ERK1/2的影响,探索其抗肝纤维化的可能机制.方法♂SD大鼠55只,体质量180-220 g,随机分为正常组、模型组、预防组.除正常组外,其余均采用四氯化碳、高脂饮食及乙醇复合因素复制肝纤维化模型,造模同时预防组每日一次予以0.8 g/kg丹芍化纤自来水悬液灌胃,模型组、正常组予以等体积自来水灌胃,持续8 wk.造模结束后肝组织HE染色病理检查,免疫组化检测肝组织PDGFR-β、蛋白印迹检测肝组织p-ERK1/2在各组表达,生化法检测各组血清透明质酸(HA)、层黏蛋白(LN)、Ⅲ型前胶原(PⅢP)、白蛋白(ALB)、总蛋白(TP),计算白球比(A/G).结果造模8 wk后经病理学证实模型大鼠形成典型的肝纤维化,模型成功.与正常组相比,模型组肝组织PDGFR-β、p-ERK1/2及血清HA、LN、PⅢP均有显著升高,ALB、A/G显著降低(PDGFR-β1 84.6±8.5 vs 89.6±5.8,P＜0.05;p-ERK1/2360.0±14.5 vs 15.4±2.1,P＜0.05;HA517.5±91.5 μg/L vs 254.4±33.1 μg/L,P＜0.05;LN58.4±11.3 μg/L vs 37.3±9.8 μg/L,P＜0.05;PⅢP36.9±5.6 μg/L vs 4.7±1.5 μg/L,P＜0.05;ALB27.4±4.9 g/L vs 42.1±1.6 g/L,P＜0.05;A/G0.89±0.08 vs 1.38±0.09,P＜0.05);与模型组相比,预防组肝组织PDGFR-β、p-ERK1/2及血清HA、LN、PⅢP均有显著降低,ALB、A/G显著升高(PDGFR-β91.1±6.3vs 184.6±8.5,P＜0.05;p-ERK1/2253.8±18.2vs 360.0±14.5,P＜0.05;HA322.9±41.4 μg/Lvs 517.5±91.5 μg/L,P＜0.05;LN46.0±9.4μg/L vs 58.4±11.3 μg/L,P＜0.05;PⅢP14.5±2.4 μg/L vs 36.9±5.6 μg/L,P＜0.05;ALB37.2±2.8 g/L vs 27.4±4.9 g/L,P＜0.05;A/G1.18±0.13 vs 0.89±0.08,P＜0.05).结论PDGFR-β及p-ERK1/2在肝纤维化形成中起重要作用,丹芍化纤胶囊具有良好的预防肝纤维化形成的作用,其降低PDGFR-β及p-ERK1/2在肝组织的表达可能是其作用机制之一.     

抵抗素在非酒精性脂肪肝病中对胰岛素抵抗和肝纤维化的作用

目的:探讨抵抗素(resistin)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中对胰岛素抵抗(insulin resistin,IR)及肝纤维化的作用.方法:应用高脂饮食喂养Wistar大鼠建立NAFLD肝纤维化模型.健康♂,Wistar大鼠30只,随机分成正常对照组和模型组,各15只,分别给予普通饲料和高脂饲料喂养.分别于第15、18、21周末将对照组和模型组随机各处理5只.检测空腹血糖(FBG)、空腹胰岛素(FINS)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、Ⅳ型胶原(CⅣ)、层粘蛋白(LN)水平,采用稳态模型评估法(HOMA)评估IR(HOMA-IR);HE、VG染色及电镜观察肝组织纤维化情况.RT-PCR法检测大鼠肝组织中resistin基因mRNA表达.结果:随着高脂喂养时间的延长,HE、VG染色及电镜观察肝组织病理学显示大鼠肝脏脂肪变性及肝纤维化程度逐渐加重,NAFLD模型组HOMA-IR、PCⅢ、LN、CⅣ、HA、resistin逐渐增加,且以21wk时升高最为明显,分别为33.74g/L±10.41g/L、2.96g/L±0.76g/L、4.14g/L±1.07g/L、19.07g/L±2.78g/L、848.87g/L±204.04g/L、0.99g/L±0.10g/L,与相应时相对照组比较差异具有统计学意义(P<0.05或P<0.01).Spearman相关性分析抵抗素与HOMA-IR、PCⅢ、LN、CⅣ、HA呈显著正相关,相关系数r分别为0.77、0.80、0.68、0.67、0.76(P<0.05或P<0.01).结论:在NAFLD纤维化形成过程中,抵抗素表达升高诱导IR并促使肝纤维化的形成与进展.     

黏附分子在沙利度胺所致大鼠肝纤维化中的作用机制

目的:观察沙利度胺对大鼠实验性肝纤维化的治疗效果并探讨其作用机制.方法:四氯化碳腹腔注射制备大鼠肝纤维化模型后,应用沙利度胺(100 mg/kg)ig分别治疗2、4、6 wk作为动态观察时相点.HE染色观察肝组织病理变化,放射免疫法检测血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC Ⅲ)和Ⅳ型胶原(CⅣ)的表达,免疫组织化学法检测细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)和E-选择素(E-selectin)蛋白质的表达,逆转录聚合酶链反应法检测ICAM-1、VCAM-1和E-selectin mRNA的表达.结果:与肝纤维化组相比,沙利度胺治疗4wk、6 wk能显著降低大鼠肝组织纤维化积分,显著降低血清HA(176.6±7.5 μg/L,173.8±6.7 μg/L vs 486.9±12.4 μg/L)、LN(38.4±5.8 μg/L,34.7±7.3 μg/L vs 84.5±5.2 μg/L)、PC Ⅲ(44.3±5.5 μg/L,40.2±6.1 μg/L vs 65.0±5.6μg/L)、CⅣ(31.8±6.7 μg/L,30.4±5.7 μg/L vs 55.6±6.5 μg/L)的含量(P＜0.05),沙利度胺治疗2 wk 4 wk,6 wk组均可显著降低ICAM-1、VCAM-1和E-selectin蛋白和mRNA的表达(P＜0.05).结论:沙利度胺可通过下调ICAM-1、VCAM-1和E-selectin表达水平而发挥抗肝纤维化作用.     

血清肝纤维化指标与肝脏病理学对照观察

目的评价血清肝纤维化指标对于诊断肝脏纤维化的临床价值。方法84例肝穿确诊的慢性乙型肝炎患者,检测透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原肽(PⅢP)、层黏连蛋白(LN)水平。对肝组织纤维化病理分期与血清纤维化指标进行对比分析。结果Ⅳ-C、HA、PⅢP、LN与肝组织纤维化病理分期的相关系数分别为0.672(P<0.01)、0.316(P<0.01)、0.374(P<0.05)、0.066(P>0.05)。除LN外,其余指标水平均随着肝组织纤维化程度的加重而逐渐上升,且Ⅳ-C、HA、PⅢP的S3、S4期水平与S1、S2期比较有统计学差异(P<0.01)。S4期作为早期肝硬化诊断标准,通过ROC曲线分析Ⅳ-C、HA、PⅢP、LN的曲线下面积分别为0.901、0.764、0.756、0.434。敏感度:Ⅳ-C>PⅢP>HA>LN;特异度:HA>Ⅳ-C>PⅢP>LN。结论血清肝纤维化指标对肝组织病理纤维化程度的判断有指导意义。     

血清透明质酸、Ⅲ型前胶原氨基端肽及层黏蛋白与老年慢性心力衰竭心肌纤维化相关性研究

目的 分析老年慢性心力衰竭(CHF)患者血清透明质酸(HA)Ⅲ型前胶原肽(PCⅢP)及层黏连蛋白(LN)与CHF及其心肌纤维化的关系.方法 采用放射免疫平衡法检测老年CHF组患者39例(心功能Ⅱ级14例,Ⅲ级21例,Ⅳ级4例,纽约心脏病学会分级法NYHA)及老年心功能Ⅰ级组(NYHA)46例血清HA,PCⅢP及LN浓度.结果 血清HA,PCⅢP及LN浓度分别为CHF组(359.75±84.59),(77.88±24.67),(86.73±23.90)μg/L;心功能Ⅰ级组(211.60±54.80),(64.82±23.99),(82.26±23.98)μg/L.与心功能Ⅰ级组比较,CHF组HA浓度显著增加(P＜0.05);两组间PCⅢP及LN浓度差异不显著(P＞0.05).结论 血清HA浓度升高可提示老年CHF及其心肌纤维化.     

血清肝纤维化HA、Ⅳ-C、PCⅢ和LN联合检测在布加综合征导致的肝纤维化诊断中的价值

目的:探讨血清透明质酸(hyaluronic acid,HA)、Ⅳ型胶原(type Ⅳ collagen,Ⅳ-C)、Ⅲ型前胶原肽(type Ⅲ procollagen,PCⅢ)、层黏连蛋白(laminin,LN)检测在布加综合征(budd-chiari syndrome,BCS)导致肝纤维化诊断的价值.方法:应用化学发光法分别检测我院介入科2004-03/2012-06收治的61例BCS患者(研究组)及60例健康者(对照组)血清HA、Ⅳ-C、PCⅢ、LN含量,并进行统计学分析.结果:BCS患者血清HA、Ⅳ-C、PCⅢ、LN含量均高于对照组,差异具有统计学意义,分别为t=6.879,P<0.05;t=7.071,P<0.05;t=5.753,P<0.05;t=6.330,P<0.05.研究组进行组间比较,血清HA、Ⅳ-C、PCⅢ、LN含量差异无统计学意义(P>0.05).结论:血清HA、Ⅳ-C、PCⅢ、LN作为检测肝纤维化灵敏指标,联合检测对BCS导致肝纤维化的诊断和临床治疗具有重要意义.     

非酒精性脂肪性肝病进展性肝纤维化患者空腹血糖受损和胰岛素抵抗调查

目的 调查非酒精性脂肪性肝病(NAFLD)患者空腹血糖受损(IFG)和胰岛素抵抗情况及其与肝纤维化的关系。方法 2020年5月～2021年5月我院健康管理门诊诊治的NAFLD患者110例,接受口服葡萄糖耐量试验(OGTT)试验。计算稳态模型胰岛素抵抗指数(HOMA-IR),采用放射免疫法测定血清Ⅳ型胶原、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)和透明质酸(HA)。计算NAFLD纤维化评分(NFS),以NFS﹥0.676被定义为存在进展性肝纤维化。应用Logistic回归模型分析影响NAFLD患者发生进展性肝纤维化的因素。结果 经OGTT试验,发现本组糖耐量正常(NGT)者43例,糖耐量异常(IGT)者35例和IFG者32例;IFG组空腹血糖(FPG)、胰岛素(FINS)和HOMA-IR指数分别为(6.6±0.3)mmol/L、(10.9±2.4)μU/mL和3.2±0.9,显著高于IGT组【分别为(5.6±0.7)mmol/L、(8.5±2.2)μU/mL和2.4±0.5,P<0.05】或NGT组【分别为(5.5±0.6)mmol/L、(7.4±1.9)μU/mL和1.8±0.4...     

β胡萝卜素对酒精性肝纤维化的防治效果

目的:研究β胡萝卜素防治酒精性肝纤维化患者的效果.方法:203例受试者,其中酒精性肝纤维化67例,非酒精性肝纤维化74例,慢性肝炎肝纤维化患者62例.另选60例健康体检者.采用肝纤维化血清透明质酸(HA)、层黏蛋白(LN)、Ⅳ型前胶原(Ⅳ-C)、Ⅲ型前胶原肽(PCⅢ)、血清结缔组织生长因子(CTGF)、血小板衍生生长因子-BB(PDGF-BB)、金属蛋白酶抑制剂-1(TIMP-1)、转化生长因子-β1(TGF-β1)、彩超进行组内组间比较,分析β胡萝卜素防治酒精性肝纤维化患者的效果.结果:HA、LN、Ⅳ-C、PCIII在肝纤维化S0-S1、S2-S4期患者治疗前较健康体检者均有显著性差异(均P<0.01).治疗后,除Ⅳ-C(μg/L)S2-S4期患者较健康体检者有统计学差异外(95.57±15.47,100.16±13.70,96.89±16.41vs84.05±24.16,均P<0.05),其他均无差异.CTGF、PDGF-BB、TIMP-1、TGF-β1在肝纤维化S0-S1、S2-S4期患者治疗较健康体检者均有统计学差异(均P<0.01).治疗后,除CTGF(μg/L)、PDGF-BB(μg/L)S2-S...     

血清肝纤维化指标与肝脏病理学对照研究

评价血清肝纤维化指标诊断肝纤维化病理分期的临床价值。 6 9例肝穿确诊的慢性乙型病毒性肝炎患者 ,同时进行血清HA、Ⅳ -C、PⅢP、LN的检测。以肝活检组织纤维化病理分期为金标准对以上血清学指标的诊断价值进行分析。HA、Ⅳ -C、PⅢP、LN与纤维化分期的相关系数分别为 0 30 2 (P <0 0 1)、0 6 6 3(P <0 0 1)、0 346 (P<0 0 5 )、0 0 5 6 (P >0 0 5 )。除LN外 ,其余指标血清水平均随着肝纤维化程度的加重而逐渐上升 ,其中HA、Ⅳ -C、PⅢPS3 、S4期血清水平与S1期比较有统计学差异 (P <0 0 1)。S4作为早期肝硬化诊断标准时 ,通过ROC曲线分析HA、Ⅳ -C、PⅢP、LN的曲线下面积分别为 0 74 5、0 90 9、0 732、0 4 2 5。敏感度Ⅳ -C >PⅢP >HA >LN ;特异度HA >Ⅳ -C >PⅢP >LN。血清肝纤维化指标对肝脏纤维化程度的判断有一定的指导意义。     

慢性病毒性肝炎患者血清中瘦素与肝纤维化指标的关系

研究血清瘦素水平与慢性病毒性肝炎和肝纤维化之间的关系。用放射免疫法检测 4 5例慢性乙型肝炎(CHB)患者血清中的瘦素和肝纤维化指标的水平。发现CHB患者血清瘦素水平 (7 6 3± 2 19)ng/ml显著高于正常对照组 (3 82± 1 0 9)ng/ml,其瘦素 /BMI值也显著高于正常对照组 ,CHB患者的血清瘦素水平与肝纤维化指标层粘蛋白 (LN)、透明质酸 (HA)、Ⅲ型前胶原 (PCⅢ )和Ⅳ胶原 (ⅣC)的水平呈正相关。瘦素与慢性病毒性肝炎肝纤维化的形成密切相关     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

中国肝癌肝移植的现状与展望

肝癌行肝移植治疗的指征、效果和相关问题一直存在争论,国际上已经有数个通用的肝癌肝移植标准,如Milan标准、Pittsburgh标准、UCSF标准等等,中国的移植学家们也在纷纷探讨适合中国的肝癌肝移植标准.本文收集并分析近年来国内外的文献,结合本移植中心460例肝移植的病例,对肝癌的分期标准、晚期肝癌行肝移植的指征进行了探讨,笔者认为影响我国肝癌肝移植的主要因素有:供肝的来源、术后乙肝及肿瘤的复发及相关社会因素等.     

Recurrent nonviral liver disease following liver transplantation

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence. It is important to recognize that rates of recurrence vary according to indication and show little correlation with rates of graft loss from recurrent disease. Recurrance rates are greatest for primary sclerosing cholangitis and autoimmune hepatitis, and low reccurrance rates are reported for alcoholic liver disease and recurrent primary biliary cirrhosis. The impact of recurrent nonalcoholic fatty liver disease is not yet clear. Patients and clinicians need to be aware of the possibility of recurrent disease in the differential diagnosis of abnormal liver tests, and management stategies may require alteration to reduce the impact of disease recurrence on outcome. Finally, an understanding of which diseases do recur after transplantation and identification of the risk factors may lead to a better understanding of the pathogenetic mechanisms of these conditions.     

Chronic liver diseases as liver tumor precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.     

Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.     

非酒精性脂肪性肝病与肝移植

随着生活水平的提高,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在人群中的发病率越来越高.非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是NAFLD的最严重类型,在发达国家已成为临床上最常见的慢性肝病类型.     

药物性肝损伤合并肝脓肿

1病例捅要患者王某,男,39岁,汉族,已婚,河北省唐山市人,职业为建筑工程承包商。于2010年6月无明显诱因自觉乏力、纳差、食量减半、恶心、厌油、呕吐（非喷射样,呕吐物为胃内容物）,无发热、腹痛、腹泻、尿黄等。于当地医院查ALTl81U／L、AST109U／L、GGT386U／L,HBsAg阴性,抗HAV阴性,抗HCV阴性。腹部B超提示肝脏实质密度增高。