异甘草酸镁对刀豆蛋白A诱导的小鼠免疫性肝损伤的保护作用

异甘草酸镁是第四代甘草酸制剂,其有效成分是一种高纯度单-18-α异构体甘草酸,临床主要用于治疗肝炎.通过抗炎、保护肝细胞膜及改善肝功能的药理作用,对四氯化碳、D-氨基半乳糖等引起的化学性肝损伤模型发挥保护效应[1-2].但目的鲜见对免疫性肝损伤作用的报道,因此,本实验通过建立刀豆蛋白A(ConA)诱导的小鼠免疫性肝损伤模型,进一步探讨异甘草酸镁的疗效及部分作用机制.     

异甘草酸镁对老年人药物性肝损伤的疗效观察

目的观察异甘草酸镁治疗老年人药物性肝损伤的临床疗效。方法选取76例老年患者随机分为观察组和对照组各38例,2组均给予常规保肝治疗,观察组在对照组基础上加用异甘草酸镁注射液,疗程结束后比较2组的总有效率。结果观察组显效率为57.9%,总有效率为92.1%,明显优于对照组的36.8%和63.2%,差异有统计学意义(P0.05);且治疗后观察组肝功能指标下降更明显,差异有统计学意义(P0.01)。结论异甘草酸镁能提高常规治疗老年人药物性肝损伤的临床疗效,且具有良好的安全性。     

异甘草酸镁治疗急性药物性肝损伤的疗效观察

为探讨异甘草酸镁对药物性肝损伤的疗效,应用异甘草酸镁对药物性肝损伤患者进行了临床观察,现报告如下。1资料与方法1.1诊断标准药物性肝损伤采用1990年国际标准[1]:血清ALT(丙氨酸转氨酶)或DBil(结合胆红素)升高至正常值上限2倍以上,或AST(天门冬氨酸转氨酶)、ALP(碱性磷酸酶)     

白藜芦醇对脓毒症大鼠急性肝损伤的保护作用

目的观察白藜芦醇对脓毒症大鼠急性肝损伤的保护作用。方法40只SD大鼠随机分为假手术组(10只)和造模组(30只),造模大鼠术后随机分为脓毒症模型组和白藜芦醇干预组,每组15只,干预组尾静脉注射无菌白藜芦醇(40 mg/kg),其余尾静脉注射等量生理盐水。ELISA法检测TBil、AST、ALT、TNF-α和IL-6表达。Western blot检测肝组织细胞核P65的表达。结果造模前三组TBil、AST、ALT、TNF-α和IL-6表达水平无显著性差异(P>0.05),造模24h后假手术组TBil、AST、ALT、TNF-α和IL-6无显著性变化(P>0.05),而白藜芦醇干预组TBil、AST、ALT、TNF-α和IL-6表达显著低于脓毒症模型组(P<0.01)。肝组织细胞核P65相对灰度值在假手术组、脓毒症模型组和白藜芦醇干预组为0.22±0.05、0.48±0.11、0.34±0.07,各组间具有显著性差异(P<0.01)。结论白藜芦醇下调了脓毒症大鼠肝组织细胞核P65蛋白的表达,抑制炎症反应,对肝损伤具有保护作用。     

罗格列酮对大鼠重症急性胰腺炎NF-κB和ICAM-1的作用

目的探讨大鼠重症急性胰腺炎（SAP）时罗格列酮对核因子-κB（NF-κB）和细胞间黏附分子-1（ICAM-1）的作用。方法急性胰腺炎模型组（SAP组）逆行胆胰管注射牛磺胆酸钠建立大鼠SAP模型;假手术组（SO组）逆行胆胰管注射等量生理盐水;罗格列酮组（R组）于造模前30min给予罗格列酮。检测血清淀粉酶（AMY）的变化,取胰头部胰腺组织行病理学检查;免疫组化检测胰腺组织NF-κB和ICAM-1的表达情况。结果SAP组各时间点AMY、胰腺组织病理评分及NF-κB和ICAM-1的表达较SO组增高（P〈0．01）;R组各时间点上述指标较SAP组均下降,但仍高于SO组（P〈0．01）;NF-κB和ICAM-1两者在SAP组和R组具有相关性（P〈0．01）。结论罗格列酮能减轻大鼠SAP胰腺病理损伤,其机制可能与通过抑制NF-κB的活性、降低ICAM-1的表达有关。     

异甘草酸镁治疗抗痨药物致药物性肝损伤患者临床疗效评价

目的：评价异甘草酸镁治疗药物性肝损伤的疗效。方法82例抗痨药物致药物性肝损伤患者被随机分为治疗组42例和对照组40例,治疗组加用异甘草酸镁注射液治疗。结果治疗前两组生化指标比较无明显差异,在治疗4周后,治疗组与对照组谷丙转氨酶、谷草转氨酶、碱性磷酸酶水平分别为（46.3±45.1）U/L对（90.2±106.6）U/L、（68.8±45.0）u/L对（100.5±32.2）U/L和（54.9±16.6）U/L对（84.0±11.3）U/L（P﹤0.01）,胆碱酯酶、总胆红素﹑谷氨酰转肽酶分别为（4182.7±301.2）U/L对（4035.1±293.0）U/L、（65.1±20.4）μmol/L对（81.8±18.4）U/L和（50.7±11.8）U/L对（82.3±21.1）U/L（P＆lt;0.05）。结论异甘草酸镁能有效治疗抗痨药物所致药物性肝损伤,能够使抗痨治疗得以继续。     

甘草酸二铵对大鼠结肠炎的抗炎作用机制研究

目的建立大鼠急性期结肠炎模型,观察甘草酸二铵(DG)对大鼠结肠炎的治疗作用,并探讨其抗炎机制。方法雌性SD大鼠分为实验组、模型组和正常对照组,每组10只。实验组、模型组大鼠用冰乙酸灌肠建立急性期结肠炎模型,实验组给予40 mg.kg-1.d-1DG干预治疗。观察疾病活动指数(DAI)、组织学变化及髓过氧化物酶(MPO)活性,免疫组化法检测核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)和细胞间粘附分子-1(ICAM-1)表达。结果实验组、模型组和正常对照组的DAI评分分别为3.5±0.6,7.1±0.8和0.5±0.4;组织学评分为3.5±0.9,6.1±1.0和1.0±0.5;MPO活性为0.72±0.08,2.02±0.10和0.22±0.04;TNF-α阳性率分别为(35.2±8.2)%,(62.5±10.1)%和(7.9±5.7)%;ICAM-1阳性率为(34.3±8.2)%,(60.2±8.3)%和(9.1±3.4)%;NF-κB阳性率为(23.3±9.2)%,(44.5±8.9)%和(9.6±4.4)%。与模型组相比,实验组的DAI、组织学及MPO活性显著改善,实验组的TNF-αI、CAM-1和NF-κB的表达显著降低,经one-way ANOVA及SNK-q检验,差异有统计学意义(P值均<0.01)。结论DG可显著改善大鼠结肠炎症,其机制可能是通过影响炎症反应的信号通路NF-κB活化及ICAM-1、TNF-α的产生和表达来抑制炎症反应。     

急性冠状动脉综合征患者外周血单核细胞核因子-κB活性变化的临床探讨

目的探讨急性冠状动脉综合征(acute coronary syndrome,ACS)患者外周血单核细胞核因子-κB(nuclear fac-tor-kappa B,NF-κB)活性的变化及其临床意见。方法分别采用免疫组织化学染色法和夹心酶联免疫吸附法测定54例ACS,42例稳定型冠心病(SCHD)患者及36例对照组的外周血单核细胞NF-κB活性和血浆可溶性细胞间黏附分子-1(sICAM-1)水平,并分析NF-κB活性与sICAM-1浓度相关性。结果ASC组NF-κB活性和sICAM-1水平显著高于稳定型冠心病组和对照组(P<0.01),而且ACS血NF-κB活性与sICAM-1水平显著正相关。但SCHD组NF-κB活性和sICAM-1水平与对照组比较,差异无显著性意义。结论急性冠状动脉综合征外周血单核细胞核因子-κB活性明显升高,NF-κB是动脉粥样斑块不稳定的标志,并可能通过上调sICAM-1表达而促发ACS。     

异甘草酸镁联合还原型谷胱甘肽治疗老年药物性肝损伤的效果观察

［摘要］　目的　观察异甘草酸镁联合还原型谷胱甘肽治疗老年药物性肝损伤的疗效。方法　选择66例老年药物性肝损伤患者随机分为两组,每组33例,对照组给予异甘草酸镁100 mg,治疗组给予异甘草酸镁100 mg+还原型谷胱甘肽1.2 g,两组均加入5%葡萄糖100 ml(或0.9%生理盐水100 ml)静脉滴注,1次/d,连用15 d。观察比较两组丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、γ-谷氨酰转移酶（GGT）、碱性磷酸酶（ALP）等指标治疗前后的变化情况。结果　治疗组较对照组在恢复肝脏功能方面疗效较好,两组比较差异有统计学意义(P<0.05)。结论　异甘草酸镁联合还原型谷胱甘肽治疗老年药物性肝损伤疗效较好。     

异甘草酸镁与复方甘草酸单胺治疗药物性肝损伤患者疗效比较研究

目的 分析比较异甘草酸镁与复方甘草酸单胺治疗药物性肝损伤(DILI)患者的疗效。方法 2018年1月～2020年1月我院收治的DILI患者102例,随机分为观察组51例和对照组51例,分别给予异甘草酸镁或复方甘草酸单胺静脉滴注治疗14～28 d。采用放射免疫法检测层粘连蛋白(LN)、透明质酸酶(HA)、III型前胶原(PC-III)和IV型胶原(IV-Col)水平,采用ELISA法检测超氧化物歧化酶(SOD)、一氧化氮(NO)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。结果 治疗后,观察组血清ALT和AST水平分别为(42.7±12.5)U/L和(38.2±9.4)U/L,显著低于对照组【分别为(64.5±21.9)U/L和(55.6±15.2)U/L,P<0.05】;血清HA、PC-III和IV-Col水平分别为(138.2±21.5)mg/L、(85.6±17.4)μg/L和(141.5±16.4)μg/L,显著低于对照组【分别为(182.1±23.9)mg/L、(123.8±19.4)μg/L和(175.4±18.7)μg/L,P<0.05】;血清SOD...     

Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats

To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels ( p < 0.01), higher serum albumin level, and reduced increase in narcotic-induced sleeping time. Thus, setarud showed protective activity against CCl4-induced hepatotoxicity in rats. Further studies of its efficacy in liver disease are warranted.     

Protective effects of chitosan oligosaccharide and its derivatives against carbon tetrachloride-induced liver damage in mice.

The protective effects of chitosan oligosaccharide (COS), d-glucosamine (GlcNH(2)) and N-acetyl-d-glucosamine (GlcNAc) on carbon tetrachloride (CCl(4))-induced hepatotoxicity and the possible mechanisms that involved were investigated in male ICR mice. CCl(4) (20mg/kg body weight, i.p.) administration induced marked increase in serum AST and ALT activities, primed liver lipid peroxidation, depleted sulfhydryl content, impaired total antioxidant capabilities and induced genotoxicity 24h after administration. Pretreatment with COS, GlcNH(2), and GlcNAc (1.5g/kg body weight, i.g.) for 12 consecutive days prior to CCl(4) challenge significantly induced metallothionein (MT) expression. Thus, the antioxidant defensive system in the body was strengthened to counteract the oxidative damage induced by the succedent CCl(4) administration. Serum AST and ALT activities were effectively decreased. Hepatic malondialdehyde formation was inhibited and sulfhydryl contents, total antioxidant capabilities were markedly restored. Genotoxicity as reflected by DNA fragmentation, however, was not mitigated by pretreatment with COS, GlcNH(2), and GlcNAc. Histophathologic results of liver also confirmed their hepato-protective effects. Pretreatment with COS, GlcNH(2), and GlcNAc also could significantly decrease serum creatinine and uric acid levels and inhibit lipid peroxidation in kidney homogenate. Our results suggest that pretreatment with COS, GlcNH(2), and GlcNAc can efficiently protect mice against CCl(4)-induced toxicity.     

Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice

AIM: To assess the effects of dihydromyricetin(DHM) as a hepatoprotective candidate in reducing hepatic injury and accelerating hepatocyte proliferation after carbon tetrachloride(CCl4) treatment.METHODS: C57 BL/6 mice were used in this study. Mice were orally administered with DHM(150 mg/kg) for 4 d after CCl4 treatment. Serum and liver tissue samples were collected on days 1, 2, 3, 5 and 7 after CCl4 treatment. The anti-inflammatory effect of DHM was assessed directly by hepatic histology detection and indirectly by serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), albumin, and superoxide dismutase(SOD). Inflammatory cytokines, such as interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α), were detected using ELISA kits. Proliferating cell nuclear antigen(PCNA) staining was used to evaluate the role of DHM in promoting hepatocyte proliferation. Hepatocyte apoptosis wasmeasured by TUNEL assay.Furthermore,apoptosis proteins Caspases-3,6,8,and 9 were detected by Western blot.SP600125 were used to confirm whether DHM regulated liver regeneration through JNK/TNF-αpathways.RESULTS:DHM showed a strong anti-inflammatory effect on CCl4-induced liver injury in mice.DHM could significantly decrease serum ALT,AST,IL-1β,IL-6 and TNF-αand increase serum albumin,SOD and liver SOD compared to the control group after CCl4 treatment(P0.05).PCNA results indicated that DHM could significantly increase the number of PCNA positive cells compared to the control(348.9±56.0 vs 107.1±31.4,P0.01).TUNEL assay showed that DHM dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control(365.4±99.4 vs 90.5±13.8,P0.01).Caspase activity detection showed that DHM could reduce the activities of Caspases-8,3,6 and 9 compared to the control(P0.05).The results of Western blot showed that DHM increased the expression of JNK and decreased TNF-αexpression.However,DHM could not affect TNF-αexpression after SP600125 treatment.Furthermore,DHM could significantly improve the survival rate of acute liver failure(ALF)mice(73.3%vs 20.0%,P0.0001),and SP600125 could inhibit the effect of DHM.CONCLUSION:These findings demonstrate that DHM alleviates CCl4-induced liver injury,suggesting that DHM is a promising candidate for reversing liver injury and ALF.     

异甘草酸镁对肝切除术后的保肝作用

目的:探讨异甘草酸镁对肝切除术后肝功能的保护作用.方法:肝切除病例64例,随机分为试验组和对照组,试验组手术开始时给予异甘草酸镁150mg,术后连续用药7 d,对照组为空白对照.分别于术前和术后1、3、7 d测定空腹外周静脉血清ALT、AST、TBIL、DBIL、GGT、ALP的含量.结果:试验组术后ALT、AST(除了第3天)明显低于对照组(P<0.05或0.01),至术后第7天时,试验组有20例患者的血清ALT水平降至正常(64.5%),试验过程中未出现假性醛固酮症等不良反应.结论:异甘草酸镁可降低肝切除术后肝酶尤其是血清转氨酶的急剧增高,减少并发症的发生,适合在肝脏围手术期使用.     

Distribution and isoforms of epimorphin in carbon tetrachloride-induced acute liver injury in mice

BACKGROUND AND AIM: Epimorphin, a morphoregulatory factor essential to organ development, is believed to direct normal morphogenesis in tissue repair. We examined the dynamics and the roles of epimorphin, a cell surface-associated molecule detected on mesenchymal cells, in hepatic tissue repair from acute liver injury. METHODS: After acute liver injury was induced by carbon tetrachloride in Balb/c mice, the distribution of epimorphin-expressing cells was studied immunohistochemically. To clarify interactions between epimorphin expression and hepatocyte behavior, epimorphin-expressing cells and proliferating hepatocytes were counted. Then, epimorphin quantity and isoforms were assessed by western blotting. To better understand effects of epimorphin, we cultured rat hepatocytes in its presence. RESULTS: Epimorphin was distributed in relation to sinusoids, portal veins, central veins and granulomas, expressed in stellate cells and myofibroblasts. In the periportal zone, the expression in sinusoids was decreased at 24 h but increased on day 7 after carbon tetrachloride administration. Numbers of epimorphin-expressing cells and proliferating hepatocytes changed in an inverse manner as time progressed. In the pericentral zone, reactivity for epimorphin was markedly enhanced concurrently with appearance of granulomas. Quantities of 34-kDa isoform paralleled epimorphin-staining intensity. In vitro, epimorphin induced spherical hepatocyte aggregates and maintained differentiated hepatocyte function. CONCLUSIONS: Epimorphin is involved in tissue repair following a single injection of carbon tetrachloride, in which distribution and the quantity of epimorphin expression are important, particularly in maintaining hepatocyte function.     

Protective effect of fufanghuangqiduogan against acute liver injury in mice

AIM: To study the effects and possible mechanisms of fufanghuangqiduogan (FFHQ) in mice with acute liver injury (ALI). METHODS: ALI was successfully induced by injecting carbon tetrachloride (CCl4) intra peritoneally and by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice, respectively. Each of the two model groups was divided into normal group, model group, FFHQ (60, 120 and 240 mg/kg) treatment groups, and bifendate treatment group. At the end of the experiment, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in liver homogenate were measured by biochemical methods. The activities of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were determined by radio-immunoassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS: In the two models of ALI, FFHQ (60, 120, 240 mg/kg) was found to significantly decrease the serum transaminase (ALT, AST) activities. Meanwhile, FFHQ decreased MDA contents and upregulated the lower SOD and GSH-px levels in liver homogenate. Furthermore, in immunologic liver injury model, FFHQ decreased levels of TNF-α and IL-1 in serum. Histologic examination showed that FFHQ could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. CONCLUSION: FFHQ had protective effect on liver injury induced by either CCl4 or BCG+LPS in mice, and its mechanisms were related to free radical scavenging, increasing SOD and GSH-px activities and inhibiting the production of proinflammatory mediators.     

补肾养肝合剂对四氯化碳诱导大鼠急性肝损伤的防护作用

目的：探讨补肾养肝合剂萃取物对四氯化碳（CCl4）诱导大鼠急性肝损伤之影响。方法：用CCl4诱导急性肝损伤模型，造模前口服补肾养肝合剂萃取物（100，500mg／kg），适时检测血清中ALT、AST活性。结果：补肾养肝合剂可有效降低CCl4诱发之ALT、AST活性；提升肝脏中抗氧化酵素（酶）SOD、GPx、GR活性。结论：结果显示补肾养肝合剂萃取物对CCl4诱导急性肝损伤具有防护作用，其防护CCl4诱导急性肝损伤之机转与提升肝脏内抗氧化酵素（酶）GR、GPx与SOD活性有关。     

四氯化碳诱导小鼠急性肝损伤模型的建立和优化

目的通过单次腹腔注射不同剂量的四氯化碳(CCl4)致小鼠急性肝损伤,检测小鼠血浆转氨酶水平的变化,建立适合本研究的小鼠模型。方法采用6~8周龄雄性C57BL/6小鼠单次腹腔注射CCl4诱导急性肝损伤。比较不同剂量的CCl4诱导急性肝损伤小鼠的血浆转氨酶水平。将182只小鼠随机分出32只。32只小鼠随机分为3组CCl4实验组(每组8只)和正常对照组(8只),分别腹腔注射0.1%、0.2%、0.3%的CCl4橄榄油溶液(10 ml/kg)或等体积橄榄油。注射12小时后取血,检测血浆丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的水平。比较0.1%和0.2%剂量组小鼠不同时间点血浆转氨酶水平的变化。将剩余150只小鼠随机分为正常对照组(10只)、实验Ⅰ组(0.1%剂量,70只)、实验Ⅱ组(0.2%剂量,70只),实验组小鼠在造模6、12、16、20、24、48、72小时后取血,检测血浆ALT、AST的水平。结果与正常对照组相比,分别用0.1%、0.2%、0.3%CCl4处理后12小时小鼠血浆ALT、AST均明显升高(P0.05),并呈剂量依赖性。与正常对照组相比,0.1%和0.2%剂量组小鼠血浆ALT、AST的水平在早期均呈上升趋势,并分别在16小时和20小时达到高峰,随后逐渐下降,在72小时接近至正常水平。结论单次腹腔注射CCl4诱导小鼠急性肝损伤呈剂量依赖性。0.1%剂量的CCl4以及该剂量处理后16小时是建立C57BL/6小鼠急性轻度肝损伤的合适剂量与检测转氨酶水平的合适时间点。     

Protective effects of Foeniculum vulgare root bark extract against carbon tetrachloride-induced hepatic fibrosis in mice

AIM To investigate the protective effects of Foeniculum vulgare root bark(FVRB), a traditional Uyghur medicine, against carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups(n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected(i.p.) with 0.1% CCl4-olive oil mixture at 10 m L/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB(88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), hexadecenoic acid(HA), laminin(LN), glutathione(GSH), superoxide dismutase(SOD), and malondialdehyde(MDA) in liver tissues were measured. Hematoxylin-eosin(H and E) staining and Masson trichrome(MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor β1(TGF-β1), matrix metalloprotein 9(MMP-9) and metallopeptidase inhibitor 1(TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-β1 and alpha-smooth muscle actin(α-SMA) protein expression was measured by Western blot.RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-β1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-β1 and α-SMA detected by Western blot was decreased by FVRB treatment.CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.