枳鳖胶囊抗大鼠肝纤维化形态学及肝组织Ⅲ型胶原mRNA表达的实验研究

目的:观察枳鳖胶囊抗肝纤维化形态学和Ⅲ型胶原mRNA表达的变化。方法:选择66只健康清洁级SD大鼠,雌雄各半,随机分为:正常对照组,模型组,秋水仙碱组,枳鳖胶囊大、中、小剂量组。以40%四氯化碳花生油皮下注射结合高脂饲料、酒水饮料复合因素诱导大鼠肝纤维化模型。造模结束后,除正常组不予处理外,其他组分别以蒸馏水,秋水仙碱混悬液,高、中、低浓度枳鳖胶囊溶液灌胃,疗程36d。疗程结束后,观察大鼠新鲜肝脏的表面情况、色泽、质地等大体形态,测定肝组织Ⅲ型胶原mRNA的表达,光镜观察肝组织HE染色和网状纤维染色的病理形态学改变。结果:模型组大鼠肝细胞损害、肝脏脂肪变性和胶原纤维增生的程度最显著,Ⅲ型胶原mRNA的表达最强。枳鳖胶囊组上述改变明显减轻,且可抑制Ⅲ型胶原mRNA的表达,疗效优于秋水仙碱组。结论:枳鳖胶囊可较好地保护肝细胞,并能阻止肝纤维化进程甚或逆转肝纤维化病理改变,抑制胶原基因表达,抑制胶原基因表达可能是其抗肝纤维化的作用机理之一。     

软肝丸治疗慢性血吸虫肝纤维化200例临床观察

目的 观察软肝丸对慢性血吸虫肝纤维化的疗效。方法 用软肝丸治疗慢性血吸虫肝纤维化病人200例，观察治疗前后肝脏的B超影像学改变。结果 治疗24周后，软肝丸组肝脏影像学有明显改善或恢复正常，与对照组比较，差异具有显著性（P〈0．05）。结论 软肝丸可明显改善慢性血吸虫肝纤维化。     

前列地尔注射液对慢性肝病血清透明质酸、IV型胶原、Ⅲ型前胶原的影响

目的　观察前列地尔注射液改善慢性肝病的炎症及抗肝纤维化的作用。方法　 42 5例慢性肝病随机分为治疗组 2 2 0例 ,对照组 2 0 5例 ,两组均采用相同的基础疗法。治疗组加用前列地尔 2 0ug加入 1 0 %葡萄糖 2 50ml,缓慢静脉滴注 ,每天 1次 ,1疗程结束复查透明质酸 (HA)、Ⅲ型前胶原 (PC -Ⅲ )、Ⅳ型胶原 (1V -C)、谷丙转氨酶(ALT) ,总胆红素 (TB) ,白蛋白 (A) ,球蛋白 (G)。结果　两组治疗前后比较P <0 .0 0 1 ,治疗组在降HA、PC -III、IV -C及改善肝功能方面明显优于对照组P <0 .0 0 1。结论　前列地尔对降低慢性肝病HA、PC -Ⅲ、IV -C有确切疗效     

Detection of liver fibrosis with magnetic cross-relaxation

The utility of MRI using magnetization transfer (MT) enhanced pulse sequences to diagnose hepatic cirrhosis in a rat model was investigated. Hepatic T₁ was measured with and without MT off-resonance RF pulses in 17 treated and six control rats. The livers were evaluated histologically, and the hydroxyproline content quantitatively measured. We did not find a statistically significant linear correlation between the MR relaxation times and the degree of tissue injury. However, the MR measurements performed with MT were superior to those without differentiating the treated and control groups. Specifically, the T₁ times were 695 ±76 ms for the treated group, versus 748 ± 61 ms in the controls; P= 0.095. The T_1sat times were also lower in the treated group, with statistical significance: 367 ± 51 ms versus 421 ± 38 ms, P = 0.016. Finally, the change in the relaxation rates (the inverse of the relaxation times) with and without saturation were 1.31 ± 0.22 s^?1 (treated group) versus 1.05 ± 0.12 s^?1 (controls), which differed significantly, P= 0.001.     

Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers.

BACKGROUND: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver. METHODS: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell-cell interactions are preserved, which closely mimics the in vivo situation. RESULTS: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected. CONCLUSIONS: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects.     

乙肝Ⅲ号合近红外信息辐照治疗乙型肝炎肝纤维化的临床研究

目的：观察乙肝Ⅲ号合近红外信息辐照治疗乙型肝炎肝纤维化的疗效。方法：选择乙型肝炎肝纤维化住院病人234例，分为乙肝Ⅲ号治疗组(76例)、近红外信息辐照组(73例)和联合治疗组(85例)。在基础治疗(包括甘利欣，复方丹参液等)上采用单纯的中药外敷、肝病治疗仪近红外信息辐照以及两联合治疗等三种不同方法，观察各组患临床症状、体征、肝功能以及相关指标如PGA、肝纤三项(透明质酸(HA)、层黏蛋白(LN)、CⅣ型胶原(CⅣ))、肝血流的变化。结果：3组皆能改善临床症状，但以联合治疗组为；3组肝功能复常比较，差异有显性，但组间比较，差异无显性；在改善PGA、肝纤三项和肝血流量方面，联合治疗组优于乙肝Ⅲ号治疗组和近红外信息辐照组。结论：乙肝Ⅲ号合近红外信息辐照对乙型肝炎肝纤维化有一定的治疗作用，且较单一方法疗效明显。     

生三七对肝纤维化小鼠血液流变学的影响

目的:观察生三七对肝纤维化小鼠血液流变学的影响。方法:复制小鼠中毒性肝纤维化模型,生三七粉灌胃6周,检测全血粘度、血浆粘度、红细胞压积等血液流变学参数,并行肝脏病理组织切片检测。结果:与空白对照组比较,肝纤维化模型组小鼠全血粘度、血浆粘度、红细胞压积明显增高(P<0.05,P<0.01),生三七治疗后小鼠全血粘度、血浆粘度、红细胞压积明显降低(P<0.05,P<0.01);肝脏病理组织切片显示使用生三七后,肝纤维化程度有明显改善。结论:生三七可降低血液粘度,延缓肝纤维化的发展。     

Resolution of skin fibrosis and joint contractures in aggressive diffuse systemic sclerosis using autologous stem cell transplantation

The use of haematopoietic stem cell transplantation (HSCT) has now expanded beyond the domain of haematological diseases. Increasingly, the benefits of intense immunosuppression in the management of severe autoimmune diseases are being recognized. In diffuse systemic sclerosis (SSc), there has been increasing evidence of the efficacy of HSCT in improving morbidity and mortality. We present the first Australian patient to undergo autologous HSCT for SSc and review the current literature in the use of HSCT in SSc. Remarkably, the patient had complete resolution of skin disease (modified Rodnan skin score 27/51–0/51), tenosynovitis, synovitis and myositis.     

早期大剂量甲泼尼龙联合环孢素A冲击治疗对口服百草枯中毒患者预后的影响

目的 观察早期大剂量甲泼尼龙联合环孢素A冲击治疗对口服百草枯(PQ)中毒患者病死率、肺纤维化发生率的影响.方法 38例口服PQ中毒患者除常规给予洗胃、血液灌流等治疗外,早期给予大剂量糖皮质激素联合免疫抑制剂(环孢素A)冲击治疗.定期监测动脉血气分析、胸部CT、肝肾功能等指标.分析口服PQ中毒患者的病死率、肺纤维化的发生率.结果 38例PQ中毒患者中死亡13例,病死率为34.2%,其中12例患者在服毒后1周内死于多器官功能衰竭,另1例死于肺纤维化.25例存活者中,有18例在住院期间发生不同程度的氧合下降,其中17例胸部CT提示肺部间质性改变,13例出现两个以上脏器(肺、肝、肾)功能损伤.25例存活患者出院后随访1个月未诉特殊不适.结论 早期大剂量甲泼尼龙联合环孢素A冲击治疗可改善PQ中毒患者的预后,但进一步明确此方法 的疗效需开展大样本的随机、双盲对照研究.     

Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human kidney disease and is caused by germline mutations in PKD1 (85%) or PKD2 (15%). It has been estimated that around 1% of tubular cells give rise to cysts, and cell hyperproliferation has been noted to be a cardinal feature of cystic epithelium. Nevertheless, it is uncertain whether the increase in proliferative index observed is an early or late feature of the cystic ADPKD kidney. METHODS: Two Pkd2 mouse mutants (WS25 and WS183) have been recently generated as orthologous models of PKD2. To determine the effect of Pkd2 dosage on cell proliferation, cyst formation and renal fibrosis, we studied renal tissue from Pkd2(WS25/WS25) and Pkd2(+/-) mice by histological analysis. We also examined the proliferative index in archival nephrectomy tissue obtained from patients with ADPKD and normal controls. RESULTS: The proliferative index of non-cystic tubules in Pkd2 mutant mice as assessed by proliferating cell nuclear antigen and Ki67-positive nuclei was between 1-2%, values 5-10 times higher than control tissue. Similarly, the proliferative index of non-cystic tubules in human ADPKD kidneys was 40 times higher than corresponding controls. In Pkd2 mutant mice, significant correlations were found between the fibrosis score and the mean cyst area as well as with the proliferative index. Of significance, proliferating tubular cells were uniformly positive for polycystin-2 expression in Pkd2(+/-) kidney. CONCLUSION: These results suggest that an increase in cell proliferation is an early event preceding cyst formation and can result from haploinsufficiency at Pkd2. The possible pathogenic link between tubular cell proliferation, interstitial fibrosis and cyst formation is discussed.