复方黄根对四氯化碳所致大鼠慢性肝损伤的保护作用

[目的]研究复方黄根对大鼠慢性肝损伤的保护作用及可能机制.[方法]制备大鼠四氯化碳(CCl4)慢性肝损伤模型,观察复方黄根对肝损伤大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)活性,总蛋白(TP)、清蛋白(Alb)和羟脯氨酸(Hyp)水平的变化以及肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响,放免法检测透明质酸(HA)、Ⅲ型前胶原肽(PⅢP)水平,免疫组化法测肝组织转化生长因子-β1(TGF-β1)的表达,并观察肝组织病理学改变.[结果]复方黄根可显著降低CCl4所致大鼠慢性肝损伤血清中ALT、AST、HA、PⅢP、Hyp水平,升高血清中Alb、TP水平;升高肝组织中SOD、GSH-Px的活性,并可降低MDA的水平;免疫组化结果表明复方黄根能抑制TGF-β1表达;病理观察结果能减轻慢性肝损伤的肝脏损伤程度.[结论]复方黄根有明显的保肝和抗肝纤维化作用,其作用机制可能与抗脂质过氧化和抑制肝组织TGF-β1的表达有关.     

姜黄素对CCl4所致急性肝损伤大鼠的保护作用及其机制研究*

目的 观察姜黄素对四氯化碳（CCl₄）所致急性肝损伤大鼠的保护作用,并研究其作用机制。方法 将60只SD大鼠随机分为对照组、模型组、水飞蓟素组（100 mg.kg^-1）和大、中、小剂量姜黄素组（100、50和25 mg.kg^-1）,每组10只。建模成功后隔日给药灌胃,共30 d。取下腔静脉血和肝组织,分别检测血清乳酸脱氢酶（LDH）和前列腺素E2（PGE2）水平,采用Bio-Rad公司试剂盒检测肝组织匀浆白介素-6（IL-6）、肿瘤坏死因子α（TNF-α）和环氧合酶-2（COX-2）水平。结果 对照组大鼠肝小叶结构完整清晰,肝细胞无坏死及脂肪变性,模型组肝组织损伤明显,经姜黄素处理肝组织炎性细胞浸润减少,肝组织损伤有不同程度的减轻;模型组大鼠血清LDH水平为（6458.00±423.72）IU/L,PEG2水平为（130.02±4.30）pg/ml,显著高于对照组[（1375.00±67.45） IU/L和（51.27±0.86）pg/ml,P<0.001],而各剂量姜黄素处理组和水飞蓟素组均可显著降低大鼠血清LDH和PGE2 水平（P<0.05）; 模型组大鼠肝组织匀浆IL-6、TNF-α和COX-2水平显著高于对照组（P<0.05）,而大中小剂量姜黄素处理组和水飞蓟素处理组肝组织IL-6、TNF-α和COX-2水平显著低于模型组（P<0.05）。结论 姜黄素对CCl4所致大鼠急性肝损伤具有保护作用,其机制可能是抑制了IL-6、TNF-α、COX-2和PGE2等炎性细胞因子的释放。     

Mechanism of protective action of bicyclol against CCl-induced liver injury in mice.

Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes.     

柳叶蜡梅提取物对小鼠急性酒精性肝损伤的保护作用

目的：研究柳叶蜡梅提取物对小鼠急性酒精性肝损伤是否具有保护作用。方法雄性C57BL/6小鼠分为4组,每组10只。对照组为正常C57BL/6小鼠;模型组用75％酒精溶液（8 mL/kg）灌胃,每天一次,连续4 d ,建立急性酒精性肝损伤模型;柳叶蜡梅组用柳叶蜡梅提取物（12 g/kg ）溶于生理盐水后灌胃,每天两次,连续11 d;实验组先按柳叶蜡梅组方法灌胃11 d ,同时在最后4 d按模型组方法建立急性酒精性肝损伤模型。通过比较各组血清ALT和AST水平,并评价肝组织病理损伤程度,观察柳叶蜡梅提取物对小鼠急性酒精性肝损伤的保护作用。结果柳叶蜡梅提取物可明显减轻酒精所致急性肝损伤,实验组小鼠血清ALT[（148．75±13．30） U/L]、AST [（170．75±16．96） U/L]与模型组ALT[（260．75±27．35） U/L]、AST[（337．75±37．68） U/L]相比明显降低,肝组织病理损伤和炎症反应减轻（P＜0．05）。结论柳叶蜡梅提取物在小鼠急性酒精性肝损伤中起到保护作用,可能成为急性酒精性肝损伤的新的治疗策略。     

糖皮质激素治疗重症药物性肝损伤的临床研究

目的探索糖皮质激素治疗重症药物性肝损伤的疗效和安全性。方法 37例重症药物性肝损伤患者分为激素治疗组16例和对照组21例。对照组采用常规保肝、退黄药物方案;激素组在对照组治疗基础上,加用小剂量、短疗程糖皮质激素治疗,观察生化学应答情况、有效率和安全性。结果激素治疗组生化学应答较早,ALT、AST、TBil、DBil、ALP水平在治疗2周时分别为(93.2±65.6)U/L;(61.7±30.7)U/L;(168.3±98.9)μmol/L;(124.7±81.4)μmol/L;(117.2±40.1)U/L、4周时分别为(52.6±32.0)U/L;(77.4±144.1)U/L;(88.9±59.7)μmol/L;(64.7±48.4)μmol/L;(116.6±63.1)U/L均较治疗前(172.9±104.8)U/L;(264.7±169.7)U/L;(259.1±108.8)μmol/L;(182.2±82.4)μmol/L;(153.8±69.9)U/L显著降低(P均0.05);对照组治疗2周仅ALT、AST降低明显(P0.05),而TBil、DBil于治疗4周后方明显降低(P均0.05);两组GGT治疗前后均无显著改善(P0.05)。治疗4周时激素组治疗有效率、显效率均显著高于对照组(93.8%比66.7%,χ~2=11.919,P=0.001;87.5%比57.1%,χ~2=6.081,P=0.014)。两组总体不良反应发生率差异无统计学意义(P0.05)。结论早期应用小剂量、短疗程糖皮质激素,可有效地治疗重症药物性肝损伤,且安全性较好。     

急性肝损伤大鼠肠源性内毒素血症形成机理及其作用的实验研究

探讨急性肝损伤大鼠肠源性内毒素血症的形成机理及肠源性内毒素血症在急性肝损伤过程中的作用.采用皮下注射硫代乙酰胺（TAA）600 mg/kg制作大鼠急性肝损伤动物模型,取回肠内容物、肝、脾、淋巴结作细菌培养,检测血浆及回肠内容物内毒素含量.行血浆D-乳酸的检测.取肝脏和回肠作病理切片.结果显示TAA诱导大鼠急性肝损伤后,血浆及回肠内容物内毒素水平上升明显（P＜0.01）,血浆TNF-α含量升高明显（P＜0.01）,且与内毒素水平升高呈正相关（P＜0.01）.同时出现肠道菌群失调,肠道通透性增加,肠道细菌移位.回肠病理所示肠绒毛明显变短、破坏、炎性细胞浸润增多.因此肠道菌群失调、肠粘膜结构改变、肠道通透性增加及肠道细菌移位是形成肠源性内毒素血症的重要因素.内毒素可直接或通过诱导TNF-α加重肝损伤.     

Hepatoprotective impact of the bile acid receptor TGR5

During liver repair after injury, bile secretion has to be tightly modulated in order to preserve liver parenchyma from bile acid (BA)‐induced injury. The mechanisms allowing the liver to maintain biliary homeostasis during repair after injury are not completely understood. Besides their historical role in lipid digestion, bile acids (BA) and their receptors constitute a signalling network with multiple impacts on liver repair, both stimulating regeneration and protecting the liver from BA overload. BA signal through nuclear (mainly Farnesoid X Receptor, FXR) and membrane (mainly G Protein‐coupled BA Receptor 1, GPBAR‐1 or TGR5) receptors to elicit a wide array of biological responses. While a great number of studies have been dedicated to the hepato‐protective impact of FXR signalling, TGR5 is by far less explored in this context. Because the liver has to face massive and potentially harmful BA overload after partial ablation or destruction, BA‐induced protective responses crucially contribute to spare liver repair capacities. Based on the available literature, the TGR5 BA receptor protects the remnant liver and maintains biliary homeostasis, mainly through the control of inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity and sinusoidal blood flow. Mouse experimental models of liver injury reveal that in the lack of TGR5, excessive inflammation, leaky biliary epithelium and hydrophobic BA overload result in parenchymal insult and compromise optimal restoration of a functional liver mass. Translational perspectives are thus opened to target TGR5 with the aim of protecting the liver in the context of injury and BA overload.     

叶下珠对小鼠酒精性肝损伤的保护作用

目的研究叶下珠对小鼠酒精性肝损伤的保护作用。方法将30只小鼠随机分为3组:空白对照组小鼠每日以常规饲料和自来水喂养;酒精损伤组小鼠每日以白酒连续灌胃,常规饲料中拌有白酒;叶下珠保护组小鼠将白酒加浓度70%的叶下珠提取液按酒精损伤组动物灌胃。4周后,处死小鼠,取小鼠血清和肝脏测定ALT、AST、MDA、SOD等指标。结果叶下珠处理能够抑制血清谷草转氨酶(AST)、谷丙转氨酶(ALT)和肝脏的丙二醛(MDA)上升,其AST、ALT和MDA值比酒精损伤组分别下降了52.5%、41.4%和29.3%。同时叶下珠也能提高超氧化物歧化酶(SOD)的活性,处理后SOD值上升了16.3%。结论叶下珠对小鼠酒精性肝损伤有明显的保护作用。     

甲强龙治疗重型药物性肝损伤合并银屑病1例报告

1病例资料患者男性,31岁,以“全身乏力20余天,尿黄半月,皮肤、巩膜黄染1周”于2018年3月19日住院。患者既往有“银屑病”13余年,无高血压、糖尿病病史;无吸烟、饮酒史;无家族遗传倾向性疾病。于2009年6月至某中医就诊,给予服用“中药”(用药成分不详)治疗3个月,治疗期间出现腹泻,7~8次/d,黄稀便,无腹痛、皮肤黄染、恶心、呕吐等不适,治疗后皮损逐渐缩小接近正常皮肤;后因食“牛肉”诱发皮损,因皮损反复出现,2017年7月再次至当地中医就诊,给予“中药”(具体不详)治疗6个月,治疗期间大便干结,2~3次/d,量少,伴里急后重感,无腹痛、恶心、呕吐,皮损控制不佳。     

Metal‐induced oxidative damage in cultured hepatocytes and hepatic lysosomal fraction: beneficial effect of a curcumin/absinthium compound

OBJECTIVE: Metals undergo redox cycling and there is increasing evidence of free radical generation and oxidative injury in the pathogenesis of liver injury and fibrosis in metal storage diseases. The aim of the present study was to test a natural hepatoprotective compound in metal‐induced liver injury. METHODS: Hepatocytes were isolated from Wistar rats by collagenase perfusion method and cultured as such and also with α‐linolenic acid (LNA)‐bovine serum albumin (BSA). Hepatocytes were then cultured with a graded dilution of PN‐M001 (100 µg/mL and 200 µg/mL), which is a curcuma/absinthium‐containing compound, or sylibin (100 µg/mL) dissolved in dimethyl sulfoxide for 10 min before the addition of metallic salts (iron, copper and vanadium). Lysosomal fractions were prepared for lysosome fragility tests in which β‐galactosidase activity and lactate dehydrogenase (LDH) leakage were measured, as well as oxidative damage tests in the presence of hydrophilic and lipophilic free radical generators. Quenching activity by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) was also assessed. RESULTS: Malonildialdehyde accumulation in the medium showed a direct time‐course increase with incubation time. Both PN‐M001 and sylibin showed a significant protective effect against all challenge metal ions, as expressed by the half inhibition concentration (IC₅₀) against lipid peroxidation. However, on a molar ratio, sylibin seemed to be more effective than PN‐M001 in Fe‐induced peroxidative damage (P < 0.05). Both test compounds, irrespective of the concentration, significantly reduced the LDH and β‐galactosidase concentration in the lysosomal fractions. As compared with untreated lysosomal fractions challenged with the two peroxide radicals generators, either PN‐M001 or sylibin exerted significant protection However, PN‐M001 was significantly better than sylibin in suppressing acid phosphatase enzyme activity. Both compounds showed comparable and significant DPPH radical‐scavenging activity. CONCLUSION: These data support the potential clinical application of curcumin‐containing compounds.     

Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury.

BACKGROUND/AIM: The main component of Panax ginseng, which have been reported by many researchers, are ginsenoside Rb1, Rb2 and Rc. Orally administered ginsenosides are metabolized to 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by intestinal bacteria and absorbed to blood. To understand its hepatoprotective effect and its mechanism, the effects of ginsenoside Rb1 and its metabolite compound K on chemically injured HepG2 cells and mice were investigated. METHODS: Ginsenoside Rb1 and compound K were isolated from ginseng. Hepatotoxicity of HepG2 cells and mice was induced by tert-butyl hydroperoxide (t-BHP). Cytotoxicity for HepG2 cells and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for mice as markers of hepatoprotective activity were measured. RESULTS: Compound K protected HepG2 cell cytotoxicity induced by t-BHP. However, ginsenoside Rb1 did not inhibit cytotoxicity. Nevertheless, both ginsenoside Rb1 and compound K significantly inhibited the increment of ALT and AST induced by t-BHP in mice, when it was orally administered. However, intraperitoneally administered ginsenoside Rb1 did not inhibit the increment of plasma ALT and AST induced by t-BHP in mice. These compounds did not exhibit antioxidant activity. However, compound K showed the potent membrane stabilizing activity more than ginsenoside Rb1. CONCLUSION: Compound K, which was produced from ginsenosides of Panax ginseng in intestine, could protect liver injury.     

急性重症药物性肝损伤患者发病状况的回顾性研究

目的回顾性研究急性重症药物性肝损伤患者的发病状况,以期对临床用药起到指导作用。方法回顾性研究2003年5月-2013年5月广西梧州中医医院收治的急性重症药物性肝损伤的患者82例,对急性重症药物性肝损伤患者的住院诊治情况和可能导致急性重症肝损伤的药物和致死药物进行分析。结果患者的治疗方式包括行人工肝治疗和单纯药物治疗,比例分别为34.15%和65.85%。在患者治疗的过程中死亡31例(37.80%),病情恶化30例(36.59%),病情好转13例(15.85%),治愈8例(9.76%);引起肝损伤的前3类药物分别是中草药、抗结核药物和抗菌药物,致病率分别为28.05%、24.39%和14.63%,在住院期间死亡的31例患者中,也是使用中草药(35.48%)和抗结核药物(19.35%)的患者比例居多。结论急性重症药物性肝损伤致死率较高,其中,中草药和抗结核药物是导致肝损伤以及致死的主要病因,对这两种药物的临床监测需要引起重视。     

复方银杏叶胶囊对大鼠肝损伤的防护作用

目的：观察复方银杏叶胶囊（CGB）的保肝作用。方法：采用大鼠免疫性肝损伤模型，比较CGB与银杏叶提取物（GB）对大鼠肝脏功能保护作用。结果：CGB高、中刺量组大鼠血清天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、总胆红素（TBil），与模型组比较，差异均有显著性意义（P〈0．05或P〈0．01）；GB组大鼠血清ALT、ALP、TBil与模型组比较，差异均有显著性意义（P〈0．05或P〈0．01），但AST与模型组比较差异无显著性意义（P〉0．05）。结论：CGB与GB均有改善免疫性肝损伤大鼠肝功能效应，但CGB作用优于CB。     

糖皮质激素联合非生物型人工肝治疗重症药物性肝损伤疗效及安全性

目的评估糖皮质激素联合非生物型人工肝治疗重症药物性肝损伤的效果及安全性。方法对激素联合人工肝治疗的96例重症药物性肝损伤患者进行回顾性分析,记录其治疗过程及血常规、肝功能等指标,观察其有效率及并发症。结果 96例重症药物性肝损伤患者治疗有效者84例,无效12例,治疗后RBC(4.22±0.70)×109/L、Hb(127.88±22.99)g/L较前升高,差异有统计学意义(P0.05);ALT(145.48±158.94)U/L、AST(98.06±69.26)U/L、TBil(165.10±124.21)μmol/L、DBil(130.66±89.46)μmol/L、IBil(35.43±37.48)μmol/L、Alb(41.12±30.93)g/L、ALP(178.64±119.65)U/L较治疗前有明显改善,差异均有统计学意义(P0.05);BUN(5.61±2.59)mmol/L、Cre(61.00±14.36)μmol/L较前升高,差异有统计学意义(P0.05),血凝各指标较前无明显变化,差异无统计学意义(P0.05)。结论激素联合人工肝治疗重症药物性肝损伤患者,疗效肯定,安全性较好,可延缓病情进展,降低肝衰竭发生率。     

益生菌增强急性严重肝损伤粪菌移植效果

目的观察小鼠肠道菌群的变化,探讨粪菌结合益生菌移植干预急性严重肝损伤的结局。方法选雄性BALB/c小鼠40只,随机分为空白对照组10只,模型组10只,普通粪菌移植组10只,粪菌+益生菌移植组10只,除空白对照组外,其余各组给予D-氨基半乳糖(3.0 g/kg)腹腔注射制备急性严重肝损伤模型,普通粪菌移植组和粪菌+益生菌移植组在造模同时分别给予普通粪菌液和益生菌+粪菌液灌肠(1次/d),48 h后取血清用于检测丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素,取肝组织用于病理学检测。取结肠内容物用于提取DNA进行16S V3-V4区高通量测序,用生物信息学分析技术对测序结果进行可操作分类单元聚类分析,α多样性分析,β多样性分析,线性判别分析找到不同分组小鼠的结肠内容物特征性差异细菌。临床生物化学指标组间差异比较采用t检验,16S V3-V4区测序结果组间差异采用Wilcoxon检验。结果模型组小鼠血清肝脏生物化学指标高于其他3组,差异有统计学意义(P<0.05),模型组肝脏HE染色结果显示肝组织镜下呈严重炎性改变;普通粪菌移植组和粪菌+益生菌移植组较模型组明显减轻,炎症减轻。16S rRNA高通量测序分析结果显示,空白对照组小鼠群菌结构与其他3组的Shannon差异无统计学意义,Observed Species差异有统计学意义,菌群构成差异大,粪菌移植增加小鼠肠道内物种数量。β-多样性分析结果显示,空白对照组与其他3组的组间差异大于疾病组之间的组间差异,粪菌+益生菌移植组改变疾病小鼠肠道菌群结构的差异细菌多为产丁酸盐细菌。结论粪菌+益生菌增强粪菌移植治疗效果,改善肝脏炎症,增加肠道内产丁酸盐细菌数量。     

乌司他丁对GalN／LPS引起大鼠急性肝损伤的保护作用

目的观察乌司他丁（UTI）对D-氨基半乳糖（D-GaIN）／脂多糖（LPS）引起大鼠急性肝损伤的保护作用,探讨其作用机制。方法72只SD雄性大鼠进行随机对照分组实验,分为正常对照组、模型组和UTI处理组,各组再分为6h、12h、24h、48h取材4个亚组。腹腔内注射D-GalN／LPS建立大鼠急性肝损伤模型,UTI处理组则在腹腔内注射D-GalN／LPS后立即注射UTI。在相应时间点,门静脉采血检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肿瘤坏死因子α（TNF-α）、一氧化氮（NO）水平;肝组织切片观察肝脏病理形态学变化;测定肝组织丙二醛（MDA）含量,Caspase-3和Caspase-8活性。结果与模型组相比,UTI处理组血清ALT、AST水平在12h、24h和48h组均明显降低（P〈0．01）;UTI处理组TNF-α、NO水平则在6h和12h有明显降低（P〈0．01或0．05）;UTI处理组肝组织MDA含量在12h、24h和48h明显降低〈P〈0．01）;UTI处理组处理6h后Caspase-3和Caspase-8活性明显降低（P〈0．01）。结论UTI对GalN／LPS引起大鼠急性肝损伤有保护作用,主要通过其抗炎、抗氧化和抗凋亡作用。     

中药虎杖对大鼠肝脏缺血性损伤保护的形态学观察

目的研究中药虎杖煎剂在治疗大鼠肝脏缺血性损伤后肝组织的病理学改变,证实该药对急性肝脏缺血性损伤有治疗作用.方法建立大鼠常温下肝门完全阻断的模型,观察肝脏缺血损伤后虎杖组和普食组在不同的时间段肝组织的病理学改变.结果通过光镜和电镜发现,术后1 d普食组与虎杖组肝细胞肿胀,结构破坏,肝窦内皮细胞孔隙加大,内皮破坏,内皮之间可见孔道.术后4 d普食组肝小叶结构仍破坏,线粒体肿胀,颗粒变性.而虎杖组未见肝细胞坏死改变,细胞膜特化部分如桥粒、毛细胆管区微绒毛有轻微破坏.术后7 d普食组肝细胞变性仍可见,线粒体轻度肿胀,基质变化,膜结构欠清楚,粗面内质网欠规则.而虎杖组肝细胞基本恢复正常形态.结论虎杖煎剂具有改善损伤肝组织的微循环,抑制白细胞、血小板与肝脏内皮细胞的粘附,达到促进肝细胞再生、修复损伤的能力.为临床上肝脏外科围手术期的应用奠定了病理学基础.