慢性肝病患者血清层粘蛋白及透明质酸的变化

目的研究血清层粘蛋白（ＬＮ）和透明质酸（ＨＡ）对慢性肝病的诊断意义。方法检测急慢性肝炎及肝硬变患者血清ＬＮ和ＨＡ浓度，与肝功能及食管静脉曲张程度和肝脏病理进行比较。结果慢性肝炎血清ＬＮ明显高于健康者和急性肝炎，肝硬变患者血清ＬＮ升高幅度较大，是慢性肝炎（ＣＨ）患者的１．８倍（Ｐ＜０．０１）。ＨＡ以４００μｇ／Ｌ为界，ＬＮ以１５０μｇ／Ｌ为界，肝硬变同时升高者占８５．２％。ＣＨ则为９．７％，两组比较差异非常明显（Ｐ＜０．０１）。慢性丙型肝炎患者早期血清ＬＮ就显著升高，电镜观察发现丙型肝炎患者贮脂细胞及成纤维细胞增多，此种病理现象较ＣＨ患者明显。结论联合检测血清ＬＮ和ＨＡ对区分肝纤维化与肝硬变有意义     

血清铁蛋白与透明质酸和肝硬化的相关性

目的 探讨肝硬化患者血清铁蛋白(SF)与透明质酸(HA)间的相关性.方法 70例肝硬化患者,其中女性16例,男性54例,平均(46.93±13.34)岁,Child-Pugh A级15例,B级19例,C级36例,采用化学发光法检测SF及HA,对SF与HA水平进行统计并分析二者之间的关系.结果 SF在肝硬化中明显增高,随着肝硬化分级的加重,患者的SF也增高,在C级处于最高水平,不同分级间比较差异均有统计学意义(P＜0.01).HA在肝硬化中明显增高,随着肝硬化分级的加重,患者的HA也增高,不同分级之间差异有统计学意义(P＜0.01).不同分级患者的SF与HA呈显著正相关(r=0.828,P＜0.001).结论 肝硬化患者中SF与HA有显著相关性,在反映肝硬化程度上SF与HA同等重要,是反映肝纤维化程度的敏感指标.     

受试者工作特征曲线分析血小板计数与透明质酸对肝硬化的诊断价值

目的 应用受试者工作特征(ROC)曲线分析血小板( PLT)计数与透明质酸(HA)对肝硬化的诊断价值.方法 收集377例慢性HBV感染者,分为慢性乙型肝炎组233例,乙型肝炎肝硬化组144例.化学发光法检测HA,全自动血细胞分析仪检测外周血的PLT计数,进行ROC曲线分析.结果 (1 )PLT计数诊断肝硬化的ROC曲线下面积(AUC)为0.888±0.0165,截断值为91×109/L,以PLT计数≤91×109/L来预测肝硬化灵敏度为84.03％,特异度为82.83％.HA的AUC为0.920±0.0138,截断值为308nmol· ml -1·h-1),以HA ＞308 nmol·ml-1 ·h-1来预测肝硬化灵敏度为84.72％,特异度为88.84％.PLT与HA的AUC之间的差异无统计学意义(P=0.089),二指标均为诊断肝硬化的优良指标.(2)以公式log10( PLT/HA)判断两个指标联合对肝硬化的诊断价值,所得AUC为0.945±0.0113,截断值为-0.595,以log10(PLT/HA)≤-0.595来预测肝硬化灵敏度为88.19％,特异度为89.7％.AUC两两比较显示log10( PLT/HA)与PLT之间的差异有统计学意义(P=0.0008);同样log10( PLT/HA)与HA之间的差异也有统计学意义(P＜0.0001).可见PLT与HA联合检测对肝硬化诊断的灵敏度和特异度更高.结论 在慢性HBV感染者缺乏肝组织病理学检查时,联合检测PLT计数与HA对肝硬化的诊断比单—检测有更高灵敏度和特异度,临床价值更高.     

肝硬变时细胞外基质代谢的血清学研究

目的研究肝纤维化时细胞外基质代谢的血清学变化规律,以及抗肝纤维化治疗的重要性．方法实验对象２６９例分为３个观察组,即正常对照组（ｎ＝３０）ＣｈｉｌｄＡ组（ｎ＝１０３）及ＣｈｉｌｄＢ＋Ｃ组（ｎ＝１６６）．对每例观察对象作血清透明质酸（ＨＡ）,Ⅲ型前胶原肽（ＰⅢＰ）,Ⅳ型前胶原肽（ＰⅣＰ）．层粘蛋白（ＬＮ）水平测定和肝功能有关指标,如ＡＳＴ,ＡＬＴ,甘胆酸（ＣＧ）和吲哚氰绿（ＩＣＧ）潴留率等检测．结果和正常组比较,ＣｈｉｌｄＡ组及ＣｈｉｌｄＢ＋Ｃ组ＨＡ,ＰⅢＰ,ＰⅣＰ,ＬＮ以及ＡＬＴ,ＡＳＴ,ＣＧ,ＩＣＧ潴留率均值呈异常升高（Ｐ＜００１）,但ＣｈｉｌｄＡ组及ＣｈｉｌｄＢ＋Ｃ组间无统计学差异．进一步研究还发现ＰⅢＰ,ＰⅣＰ,ＨＡ以及ＬＮ等血清浓度和ＣＧ,ＩＣＧ潴留率,ＡＳＴ,ＡＬＴ间呈密切正相关,经保肝、利胆等治疗,在血清ＡＳＴ,ＡＬＴ,ＣＧ及ＩＣＧ潴留率好转后ＨＡ,ＰⅢＰ,ＰⅣＰ,ＬＮ的血清水平也呈同向变化．结论部分肝硬变患者,肝纤维化的形成仍很活跃,积极有效的保肝,利胆,抗纤维化治疗十分必要     

血清肝纤维化标志物与慢性丁型肝炎肝纤维化程度关系的探讨

目的探讨ALT、HBV DNA及血清纤维化标志物透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性丁型肝炎(CHD)患者肝纤维化程度的关系。方法收集2008年3月至2013年1月在广州市第八人民医院肝病科住院并未曾接受任何抗病毒治疗的CHD患者28例,检测患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活组织检查检测肝组织纤维化分期。HBe Ag阳性与阴性组间计量资料比较采用t检验,计数资料比较采用χ2检验,不同纤维化分期间比较采用非参数检验中的Kruskal-Wallis检验;相关性分析采用Spearman等级相关分析。结果 HBe Ag阳性与HBe Ag阴性组患者间肝纤维化程度差异无统计学意义(χ2=0.129,P=0.720)。肝纤维化S1、S2及S≥3 3组间HA及LN水平差异有统计学意义(Z值分别为12.035、8.457,P值分别为0.002、0.015),其中S≥3组患者水平最高[HA:(169.4±166.3)ng/ml,LN:(149.2±85.1)ng/ml]且与S1、S2组比较差异均存在统计学意义(P值均0.05),而3组间其他实验室指标ALT、HBV DNA、PⅢP及CⅣ水平差异均无统计学意义(P值均0.05)。肝纤维化分期与HA、LN、PⅢP及CⅣ水平呈正相关(r值分别为0.512、0.472、0.451、0.454,P值分别为0.005、0.011、0.016、0.015)。结论 HA、LN水平可能作为评估CHD患者肝纤维化程度的血清学指标。     

神经生长液对缺血性脑损伤的保护作用

目的观察神经生长液(NGD)对大鼠实验性脑缺血再灌注损伤的保护作用。方法采用大脑中动脉线栓法建立大鼠局灶性脑缺血再灌注模型,观察NGD对大鼠神经功能的恢复、血清总超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、梗死体积、病理组织损伤及细胞超微结构改变的影响。结果NGD能改善大鼠的神经功能评分,增加血清SOD活性,降低血清MDA含量,减少梗死体积(P<0.05或0.01)。NGD能改善大鼠局灶性脑缺血再灌注3d后的病理组织学损害及细胞超微结构改变。结论神经生长液对实验性脑缺血再灌注损伤具有保护作用。     

抗纤复方Ⅰ号对酒精性肝病大鼠肝星状细胞活化的影响

目的观察抗纤复方Ⅰ号对酒精性肝病大鼠肝星状细胞活化的影响,以探讨中药治疗酒精性肝病的机制.方法给予Wistar大鼠乙醇8～10g·kg-1·d-1,分3次灌胃,12周制备酒精性肝病大鼠模型,对照组给予等量生理盐水,中药组在给予同酒精组等量乙醇的基础上,给予抗纤复方Ⅰ号水煎剂4.0ml·kg-1·d-1,分2次灌胃,共12周.实验4、8、12周末分批处死动物,HE及VG染色观察肝脏组织学改变,电镜下观察肝星状细胞形态学改变并检测肝内透明质酸(HA)和层黏连蛋白(LN)含量.结果造模12周时,酒精组大鼠肝脏呈现重度脂肪变性,点片状肝细胞坏死及炎性细胞浸润,纤维条索形成;而中药组大鼠仅呈现轻度脂肪变,无纤维条索形成.电镜下酒精组大鼠肝细胞失去正常结构,星状细胞增多、变形,细胞外可见较多胶原纤维.中药组大鼠肝细胞及星状细胞形态基本正常,基质内亦可见少量胶原纤维.实验8周末酒精组LN浓度开始升高,12周末达到最高,与正常组及中药组比较差异有显著性意义[(37.69±5.01)vs(22.34±3.51)、(28.07±4.11),P＜0.05];肝内HA浓度8周末各组间比较无统计学差异,12周末酒精组明显升高,与正常组及中药组比较,差异有显著性意义[(74.85±9.23)vs(41.26±8.34)、(53.62±4.85),P＜0.01].结论抗纤复方Ⅰ号能降低肝内HA和LN,抑制酒精性肝纤维化形成,这与其抑制肝星状细胞活化有关.     

Effects of Fuzheng Huayu 319 recipe on liver fibrosis in chronic hepatitis B

AIM To investigate clinic effects of Fuzheng Huayu 319 recipe (319 recipe) on liver fibrosis in chronic hepatitis B.METHODS Ninety-five patients with chronic hepatitis B were divide into the treated (63 cases) and control (32 cases) group, and orally administrated with 0.5g 319 capsule or 0.5g Dahuang Zhachong pill tid for 3 months, respectively. The liver functions and serological fibrotic markers were observed before and after treatment, 12 cases in the treated group were examined with liver biopsy.RESULTS Three hundreds nineteen recipe could remarkably decreased serum ALT level and total bilirubin and significantly improve serum albumin and A/G ratio. Its effects were better than Dahuang Zhachong pill. Before treatment, patients' serum monamine oxidase activities, tissue inhibitor of metalloproteinase (TIMP)-1, procollagen type Ⅲ and laminin were all higher than those of health peoples. These levels decreased remarkably after treatment, and urine hydroxyproline level increased significantly (P＜0.001-0.05). Compared with the control, the improvement in treated group was better than that in the control except TIMP-1. According to the scoring system for staging of chronic hepatitis, the fibrotic extents of 7 cases among 12 cases examined by liver biopsy decreased remarkably (1 case decreased by 3 scores, 5 by 2 scores, 1 by 1 score).CONCLUSION Fuzheng Huayu 319 recipe had good therapeutic effects on chronic hepatitis B, it could reverse the development of liver fibrosis to some extent. In general its effects were better than that of Dahuang Zhachong pill.     

Effects of Fuzheng Huayu 319 recipe on liver fibrosis in chronic hepatitis B

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Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C

Changes in serum hyaluronic acid (HA) in 35 patients treated with interferon (IFN) were studied and the histological change in fibrosis was analysed. Serum HA levels and hepatitis C virus (HCV) RNA were followed from the start of therapy to 12 months after completion of treatment. Histological changes in pre- and post-treatment liver biopsies were assessed using a modified Knodell's scoring system. The serum levels of HA (r = 0.79; P<0.0001) correlated with the degree of fibrosis more closely than with that of amino terminal peptides of type III procollagen (PIIIP; r = 0.45; P<0.05) or type IV collagen (IV-C; r = 0.42; P<0.05). Only complete responders (CR) had a significant decrease in serum levels of HA and IV-C (P<0.05), in parallel with histological improvement (P<0.01). Neither partial responders (PR) nor non-responders (NR) had significant changes in histological scores and in serum levels of fibrotic markers. Significant differences were observed between CR and NR, both in HA levels (P<0.01) and PIIIP levels (P<0.05) 12 months after the cessation of treatment. These results suggest that serum HA is an indicator of the extent of fibrosis in chronic hepatitis C. Serial determinations of serum HA levels may be of use for monitoring the histological response of hepatic fibrosis to IFN treatment in chronic hepatitis C.     

Intra-articular hyaluronic acid in the treatment of haemophilic arthropathy of the knee. Clinical, radiological and sonographical assessment

Hyaluronic acid has been used successfully in the treatment of osteoarthritis since 1989. There is no experience in haemophiliacs in larger study groups. In a prospective study, 20 patients (21 knees) with haemophilic arthropathy of the knee received 20 mg hyaluronic acid by intra-articular injection for 5 consecutive weeks. Assessment included clinical scores, X-ray, magnetic resonance imaging (MRI) and biomechanical motion analysis before and 3 months after the first injection. The score of the WFH advisory committee and the Aichroth score for special evaluation of the knee were used. After an average period of 26 months, the World Federation of Hemophilia (WFH) score, the Aichroth score and the visual analogue scale were evaluated again. All patients had pain caused by their arthropathy, nine of them had positive antibodies to human immunodeficiency virus, and 15 had chronic hepatitis C. The mean WFH score was 8.1 points, the Petterson score was 7.3 points and the Aichroth score was 38 points (maximum 55 points). The WFH score decreased to 7.3 points, the Aichroth score improved to 40 points and the subjective assessment measured with a visual analogue scale improved from 5.3 to 3.7 points. No differences from MRI controls were detected. After 3 months, 14 of 20 patients improved subjectively, particularly in longer walking distance, stair-climbing or initial pain. These positive aspects were limited by arthropathy in adjacent joints. After 26 months 10 patients still are benefiting for up to 31 months follow-up. The average WFH score was 7.3 points, the Aichroth score 39 points, the visual analogue scale 4.0 points. We recommend hyaluronic acid for haemophilic arthropathy of the knee when regular conservative therapy has failed and operative treatment is not feasible.     

Morphological and serum hyaluronic acid, laminin and type Ⅳ collagen changes in dimethylnitrosamine-induced hepatic fibrosis of rats

AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type Ⅳ collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type Ⅳ collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESUJLTS: The levels of serum HA, type Ⅳ collagen and LN significantly increased from d 7 to d 28 (P = 0.043).The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with HE and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 lobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope.All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P＜0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type Ⅳ collagen.CONCLUSION: The morphological and serum HA, type Ⅳ collagen, and LN are changed in DMN-induced liver fibrosis in rats.     

Morphological and serum hyaluronic acid, laminin and type IV collagen changes in dimethylnitrosamine-induced hepatic fibrosis of rats

AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN). METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin alpha-SMA staining as well as Sirius-red and HE staining. RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with HE and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 lobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of alpha-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of alpha-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P<0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen. CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.     

A Study on the dynamic alterations of serum HA in rats with carbontetrachloride-induced liver fibrosis

AIM To study the clinical significance of alterations of serum hyaluronic acid in rats with carbontetrachioride-induced liver fibrosis.METHODS Rat liver fibrosis model was induced by carbon tetrachloride (CC14). The rats were divided intofive groups; group 1 (control): 0 week with no CCl4-inducing; group 2, 3, 4 and 5: 3, 6, 9 and 12 weeksafter CCl4-induction respectively. Serum HA level was analysed among various liver fibrosis groups andcontrol, and then compared the HA findings with the hepatic histopathology.RESULTS During rat liver fibrosis, serum HA levels of the liver fibrosis groups (group 2: 7.98ng/mL;group 3: 20.10 ng/mL; group 4:229.73 ng/mL; group 5:324,74 ng/mL) were significantly higher thanthat of control group (group 1:0.21 ng/mL) (P<0.01), in which group 4 and group 5 are much higher1094 times (229.73ng/mL/0.21 ng/mL) and 1546 times (324.74 ng/mL/0.21 ng/mL) than group 1respectively. When compared with each other, the serum HA levels are 38 times (7.98ng/mL/0.21 ng/mL; P<0.01, group 2 vs group 1); 2.5 times (20.10ng/mL/7.98 ng/mL; P<0.01, group 3 vsgroup 2); 11.4 times (229.73 ng/mL/20.10 ng/mL; P<0.01, group 4 vs group 3); 1.4 times (324.74 ng/mL/229.73 ng/mL; P<0.01, group 5 vs group 4) respectively.CONCLUSION The results demonstrated that the dynamic alterations of serum HA play an important rolein the early clinical diagnosis and staging of liver cirrhosis.     

Serum hyaluronan and aminoterminal propeptide of type III procollagen in primary biliary cirrhosis: relation to clinical symptoms, liver histopathology and outcome.

Hyaluronan (HA) and aminoterminal propeptide of type III procollagen (PIIINP), two biochemical connective tissue markers, were determined in 76 patients with primary biliary cirrhosis (PBC). The HA and PIIINP concentrations were significantly increased compared with controls (P less than 0.001). Both HA and PIIINP levels correlated significantly with conventional liver-function tests. All patients with stage IV PBC showed increased concentrations of both these variables. However, HA was a better marker with regard to prediction of development of cirrhosis as well as prediction of symptoms. Furthermore, HA also showed a negative correlation with time of survival (P less than 0.05). The present data indicate that HA is a more sensitive marker of liver damage in PBC than PIIINP.     

扁桃甙对大鼠肝贮脂细胞增殖和产生胶原的影响

目的探讨桃仁有效单体扁桃甙抗肝纤维化的作用机理．方法用链霉蛋白酶和胶原酶原位灌注大鼠肝脏，以１１％Ｍｅｔｒｉｚａｍｉｄｅ分离出贮脂细胞，传一代培养后分别加入１０－４－１０－９ｍｏｌ／Ｌ浓度的扁桃甙液温育７２ｈ，分别作细胞增殖和细胞产生胶原的测定．结果低浓度药物能减少［３Ｈ］胸腺嘧啶核苷细胞内掺入量及抑制［３Ｈ］脯氨酸掺入于细胞分泌的胶原酶敏感蛋白和细胞层胶原酶敏感蛋白中，其中尤以１０－８ｍｏｌ／Ｌ浓度最为明显，其对贮脂细胞增殖的抑制率达２５０％，培养液和细胞内胶原产生的抑制率分别为２４２％和２６８％．结论扁桃甙能抑制活化贮脂细胞的增殖和产生胶原