Artificial Liver Support System Combined with Liver Transplantation in the Treatment of Patients with Acute-on-Chronic Liver Failure

Background

The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF) remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS) combined with liver transplantation (LT) in the treatment of ACLF.

Methodology/Principal Findings

One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group) and the other 56 received emergency LT (LT group). The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2–226 days) from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%.

Conclusions/Significance

Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.     

Hepatoprotective Effects of Purple Potato Extract against D-Galactosamine-Induced Liver Injury in Rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-α), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-α, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2′-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.     

Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition

Background & Aim

To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions.

Methods

We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea.

Results

Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391).

Conclusions

The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.     

Caspase-1、OPN在慢加急性乙型肝炎肝衰竭患者血清中的表达及其临床意义

摘要 目的：探讨半胱氨酸蛋白酶-1 (Caspase-1)、骨桥蛋白（OPN）在慢加急性乙型肝炎肝衰竭（HBV-ACLF）患者血清中的表达及其临床意义。方法：选择2020年6月至2022年6月中国人民解放军联勤保障部队第九七Ο医院收治的86例HBV-ACLF患者（HBV-ACLF组）;另选取同时段接诊的58例慢性HBV感染患者（CHB组）;收集同时间段60例体检的健康志愿者（对照组）。检测所有受试者血清Caspase-1、OPN、肝功能指标水平,探讨HBV-ACLF患者血清Caspase-1、OPN水平与肝功能指标的相关性,单因素分析及Logistic多元逐步回归分析影响HBV-ACLF患者预后的危险因素。结果：三组血清Caspase-1、OPN、肝功能指标水平比较差异有统计学意义（P＜0.01）。HBV-ACLF组、CHB组血清Caspase-1、OPN、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBIL）水平高于对照组（P＜0.05）,白蛋白（Alb）、胆碱酯酶（CHE）水平低于对照组（P＜0.05）,HBV-ACLF组血清Caspase-1、OPN 、ALT 、AST 、TBIL水平高于CHB组（P＜0.05）,Alb、CHE水平低于CHB组（P＜0.05）。Pearson相关分析显示,HBV-ACLF患者血清Caspase-1、OPN水平均与ALT、AST、TBIL呈正相关（P＜0.05）,与Alb、CHE呈负相关（P＜0.05）。单因素分析显示,HBV-ACLF患者预后与肝硬化、肝性脑病、腹膜炎发生率、终末期肝病评分模型（MELD）评分、白细胞计数（WBC）、血小板计数（PLT）、肌酐（Cr）、国际标准化比值（INR）、TBIL、HBV-DNA载量（HBV-DNA）、Caspase-1、OPN有关（P＜0.05）;而与年龄、性别、血红蛋白（HGB）、BUN、ALT、AST、CHE、Alb无关（P>0.05）。Logistic多元逐步回归分析模型结果显示,HBV-DNA、MELD评分、Caspase-1、OPN是影响HBV-ACLF患者预后的危险因素（P＜0.05）。结论：HBV-ACLF患者血清Caspase-1、OPN水平呈异常高表达,且Caspase-1、OPN高表达水平与肝功能恶化和不良临床结局有关,可为HBV-ACLF患者病情进展及预后评估提供依据。     

Amelioration of Rhabdomyolysis-Induced Acute Kidney Injury by Ademetionine

Biophysics - Abstract—Using the animal model of rhabdomyolysis-induced acute kidney injury have revealed a significant nephroprotective effect of ademetionine by ability to eliminate the...     

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.     

Amelioration of Experimental Autoimmune Uveitis by Leflunomide in Lewis Rats

Purpose

To investigate the efficacy of leflunomide in experimental autoimmune uveitis (EAU) in rats.

Methods

Lewis rats were immunized with interphotoreceptor retinoid-binding peptide (IRBP) in order to generate EAU. Rats received three dose of leflunomide through intragastric administration (prevention or treatment protocols) after immunization at three separate doses (3 mg/kg/d; 6 mg/kg/d; 12 mg/kg/d). Cyclosporin A was administered as a positive) control. Rats were euthanized during peak disease activity (day 14 or 15). Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d14) and histopathological evaluation of enucleated eyes after experimental termination. The expression levels of inflammatory cytokines in the serum were quantified by ELISA. Eyeball of rats were harvested and mRNA expression of interleukin 17 (IL17) and IFN-γ were quantified through RT-PCR. Intracellular expression of interleukin (IL)-17 in the activated CD4(+) T cells was assessed by flow cytometry. The effects of leflunomide inhibition on immune responses in rats were investigated in isolated lymphocytes.

Results

Histopathological and clinical data revealed severe intraocular inflammation in the immunized rat. Inflammation reached its peak on day 14 in this EAU model. Treatment with leflunomide significantly prevented and treated EAU-induced ocular inflammation and decreased clinical and pathological scores compared to vehicle-treated eyes. Gene expression of IL17 and IFN-γwas markedly reduced in leflunomide-treated eyes. Leflunomide significantly decreased the serum levels of IL17 and IFN-γ. The study of IL17+ T cells in peripheral blood and spleen by flow cytometry showed a decreased number of Th17 cell in rats of leflunomide prevented group. Lymphocytes from animals treated with leflunomide had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals.

Conclusions

Oral administration of leflunomide effectively suppressed IRBP-induced uveitis in rats. These results suggest that leflunomide may be potentially clinical application in uveitis.     

D-半乳糖诱导大鼠肾脏损害的糖基化机制及药物干预作用

目的D-半乳糖（D-galactose）诱导大鼠体内不同糖基化水平,研究其肾脏损伤发生的机理及药物对其干预作用。方法采用不同剂量D-半乳糖[150、75、37.5 mg/（kg.d）]分别腹腔注射（ip）处理大鼠8周,诱导糖基化状态和肾脏损伤,同时D-半乳糖高剂量[150 mg/（kg.d）]分别给与氨基胍[150 mg/（kg.d）]和维生素E[150 mg/（kg.d）]处理8周。采用葡萄糖氧化酶法测定大鼠血糖,硫代巴比妥酸（TBA）比色法测定糖化血红蛋白,硝基四氮唑蓝（NBT）比色法测定血清果糖胺;按文献方法分别测定血红细胞醛糖还原酶活性和晚期糖基化终末产物（AGEs）含量及肾脏组织中AGEs含量,羟胺法和比色法分别测定SOD和GSH-Px活性,硫代巴比妥酸法测定MDA含量;采用CBB法测定尿蛋白含量,二乙酰-肟法测定血尿素氮,苦味酸法测定血肌酐;流式细胞仪检测肾脏细胞凋亡情况。结果D-半乳糖高、中剂量处理8周后,大鼠2 h血糖明显升高,血红细胞醛糖还原酶活性升高,糖化产物形成增多（P〈0.01,P〈0.05）;肾组织中AGEs含量明显升高,SOD及GSH-Px活性下降,MDA含量升高（P〈0.01,P〈0.05）,尿蛋白、血尿素氮和血肌酐量明显增加,肾脏细胞凋亡率明显增加（P〈0.01,P〈0.05）。而氨基胍和维生素E处理后,可明显抑制高剂量D-半乳糖引起的糖基化反应,减少上述物质的生成,并减轻对肾脏组织的损伤作用,尤其是氨基胍作用更为明显。结论D-半乳糖通过诱导体内蛋白糖基化和肾组织AGEs大量生成,降低抗氧化能力,诱致肾脏细胞凋亡;氨基胍和维生素E对D-半乳糖诱致的肾脏损伤作用具有保护作用。     

五味子乙素对二氧化硅致大鼠肺损伤的保护作用

目的探讨五味子乙素（schisandrin B,Sch-B）对二氧化硅致大鼠肺损伤的保护作用。方法将64只大鼠随机分为对照组、染矽尘组、Sch-B干预组。非暴露气管法建立大鼠二氧化硅矽肺模型,灌胃给予Sch-B80 mg/kg/d。药后3、7、14和21 d,对照组、染矽尘组和Sch-B干预组分别随机安乐死4、6和6只大鼠,取其肺组织,测定肺系数;光镜观测其病理8切片;紫外分光光度计检测大鼠肺组织匀浆中羟脯氨酸（hydroxyproline,HYP）、丙二醛（malondialdehyde,MDA）、谷胱甘肽（glutathione,GSH）的含量变化。结果Sch-B对矽肺病理形态学有明显的改善作用,可以降低染矽大鼠的肺系数,降低肺组织匀浆中HYP和MDA含量,提高GSH含量,与染矽尘组比较,具有统计学差异（P〈0.05或P〈0.01）。结论Sch-B可以提高机体的抗氧化能力,对二氧化硅致大鼠肺损伤具有保护作用。     

多巴胺联合NE对感染性休克致急性肝损伤大鼠肝功能、炎性因子及NF-κB p65蛋白的影响

目的:本研究通过研究多巴胺(Dopamine,DA)和去甲肾上腺素(Noradrenaline,NE)对感染性休克致急性肝损伤大鼠肝功能、炎性因子及NF-NF-κB p65蛋白的影响,以期为临床治疗提供一定的试验依据。方法:以48只SPF级健康雄性SD大鼠为研究对象,根据随机数字表法分为四组,每组12只,分别为对照组,脂多糖(lipopolysaccharide,LPS)组,NE组,DA+NE组。LPS、NE和DA+NE建立感染性休克模型,NE组静脉输注去甲肾上腺素,DA+NE组在NE组的基础上静脉输注DA。对各组大鼠肝功能、炎性因子和NF-κB p65蛋白水平进行检测。结果:与对照组相比,LPS、NE和DA+NE组血清天冬氨酸转氨酶(aspartate transaminase,AST)和丙氨酸转氨酶(alanine Transaminase,ALT)水平均显著升高(P<0.05),与LPS组相比,NE和DA+NE组大鼠血清AST和ALT均有不同程度的降低(P<0.05),与NE组相比,DA+NE组大鼠血清AST和ALT水平降低更显著(P<0.05)。与对照组相比,LPS、NE和DA+NE组血清白细胞介素6(interleukin-6,IL-6)和肿瘤坏死因子(tumornecrosis factor,TNF-α)水平均显著升高(P<0.05),与LPS组相比,NE和DA+NE组大鼠血清IL-6和TNF-α均有不同程度的降低(P<0.05),与NE组相比,DA+NE组大鼠血清IL-6和TNF-α水平降低更显著(P<0.05)。与对照组相比,LPS、NE和DA+NE组NF-κB p65蛋白表达水平均显著升高(P<0.05),与LPS组相比,NE和DA+NE组大鼠NF-κB p65蛋白表达均有不同程度的降低(P<0.05),与NE组相比,DA+NE组大鼠NF-κB p65蛋白表达水平降低更显著(P<0.05)。结论:多巴胺联合NE对对大鼠感染性休克所导致的急性肝损伤具有良好的保护作用。     

TAA 致慢性肝病内毒素血症大鼠清道夫受体、CD14 表达变化*

目的:观察清道夫受体(SR)和脂多糖受体CD14在TAA介导的慢性肝病内毒素血症大鼠肝组织中的表达。方法:通过大鼠持续灌胃给小剂量(12mg/kg.d)TAA建立大鼠肝损伤内毒素血症模型,HE染色光镜观察肝脏病理变化;改良赖氏法检测大鼠血清ALT、AST;改良过氯酸法测定血清内毒素含量;酶联免疫法检测大鼠血清CD4+和CD8+;免疫组化染色方法观察大鼠肝组织清道夫受体和CD14的表达。结果:TAA诱导后,大鼠肝脏出现片状坏死并可见灶性炎症;血浆ALT、AST及内毒素水平显著升高(P<0.05或P<0.01);血清CD4+、CD8+T细胞明显降低(P<0.01);肝组织CD14表达上调,清道夫受体表达下调,和正常大鼠相比,差异显著(P<0.05)。结论:肝组织SR表达下降和CD14表达增强可能是TAA介导慢性肝病内毒素血症的重要机制。     

Intervention of Selenium on Chronic Fluorosis-Induced Injury of Blood Antioxidant Capacity in Rats

This study was conducted to further explore the effects of selenium on the blood antioxidant capacity in rats exposed to fluoride to find out the optimal dosage level of selenium. Animals were divided into prevention sequence (Selenium?→?NaF, water?→?NaF) and treatment sequence (NaF?→?Selenium, NaF?→?water) (sodium fluoride 50?mg/L; sodium selenite 0.375, 0.75, 1.5?mg/L). The exposure time was 12?months. Then, the fluidity of erythrocyte membrane by electron spin resonance was analyzed, and the blood was collected for GSH-Px and SOD activity, total antioxidant capacity (T-AOC) and uric acid assay, sialic acid and MDA content. The results showed that, compared with control group, GSH-Px activity and T-AOC level increased significantly (P??0.05). The fluidity of erythrocyte membrane showed significant increase (P?相似文献   

Delayed Postconditioning Protects against Focal Ischemic Brain Injury in Rats

Background

We and others have reported that rapid ischemic postconditioning, interrupting early reperfusion after stroke, reduces infarction in rats. However, its extremely short therapeutic time windows, from a few seconds to minutes after reperfusion, may hinder its clinical translation. Thus, in this study we explored if delayed postconditioning, which is conducted a few hours after reperfusion, offers protection against stroke.

Methods and Results

Focal ischemia was generated by 30 min occlusion of bilateral common carotid artery (CCA) combined with permanent occlusion of middle cerebral artery (MCA); delayed postconditioning was performed by repetitive, brief occlusion and release of the bilateral CCAs, or of the ipsilateral CCA alone. As a result, delayed postconditioning performed at 3h and 6h after stroke robustly reduced infarct size, with the strongest protection achieved by delayed postconditioning with 6 cycles of 15 min occlusion/15 min release of the ipsilateral CCA executed from 6h. We found that this delayed postconditioning provided long-term protection for up to two months by reducing infarction and improving outcomes of the behavioral tests; it also attenuated reduction in 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG)-uptake therefore improving metabolism, and reduced edema and blood brain barrier leakage. Reperfusion in ischemic stroke patients is usually achieved by tissue plasminogen activator (tPA) application, however, t-PA''s side effect may worsen ischemic injury. Thus, we tested whether delayed postconditioning counteracts the exacerbating effect of t-PA. The results showed that delayed postconditioning mitigated the worsening effect of t-PA on infarction.

Conclusion

Delayed postconditioning reduced ischemic injury after focal ischemia, which opens a new research avenue for stroke therapy and its underlying protective mechanisms.     

解毒舒肝颗粒对CCL4致大鼠慢性肝损伤的保护作用研究

目的:探讨CCL_4慢性肝损伤模型大鼠肝功能指标及肝组织氧自由基代谢的变化以及解毒舒肝颗粒对其变化的影响。方法:用40?L_4花生油混合液皮下注射诱导复制慢性肝损伤模型,并用不同剂量的解毒舒肝颗粒进行干预,腹主动脉取血测定肝功能相关指标ALT、AST、ALB、TP、A/G;取肝组织匀浆测SOD、MDA、GSH-Px。结果:CCL_4急性肝损伤模型大鼠血清中AST、ALT含量均明显升高;肝组织中SOD、GSH-Px含量下降明显,MDA含量上升;解毒舒肝颗粒对上述指标有一定的逆转作用。结论:解毒舒肝颗粒对CCL_4慢性肝损伤较好的防治作用,机制可能与其抗氧化活性,清除氧自由基及调节代谢,促进肝细胞蛋白的合成有关。     

Basic and Clinical Research on the Therapeutic Effect of Intervention in Primary Liver Cancer by Targeted Intra-Arterial Verapamil Infusion

The aim of this study was assess the therapeutic effect of targeted intra-arterial verapamil infusion in liver cancer patients and its side-effects in a dog model. The blood verapamil levels in dogs were determined after one-off intra-arterial infusion (0.7 mg/kg). Blood pressure, breathing state, and II-lead electrocardiogram were measured. Primary liver cancer patients (100) were randomly assigned into two groups. Controls (50) were treated with targeted intra-arterial infusion, and every patient received once-a-month interventional therapy, twice. Treatment group (50) received chemotherapeutics plus verapamil. Therapeutic and toxic side effects were evaluated. Control (41) and treatment group (45) patients were further treated with a second round of targeted intra-arterial infusion of chemotherapeutics plus verapamil, in 30 days after the 2-time interventional therapy. Every patient accepted interventional therapy 4–5 times during the 6 months after the first confirmed diagnosis. Following verapamil infusion, verapamil in dog liver was tenfold higher than in blood and was 4- to 20-fold higher than that needed for reversing carcinoma drug resistance. After interventional therapy, there were no significant changes in iconographic evaluation indices between the groups. Average activities of aminotransferases were 332 and 178 U/l in the treatment and control groups (P < 0.05). The imaging parameters of the treatment group were significantly better than those of control group. No side effects were found among the 91 patients who accepted verapamil infusion. After verapamil infusion, verapamil levels in dog hepatic tissue exceeded the effective concentration that reverses carcinoma multidrug resistance without any visible changes in the vital signs. Targeted intra-arterial verapamil infusion could improve the chemotherapy for the primary liver cancer patients without any side effects.     

Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats

The baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interlukin-1 β (IL-1 β), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GP_X) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GP_X and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200 µg/rats/day) showed predominantly normal myocardial structure and no inflammatory cell infiltration. It has been concluded that Baobab fruit pulp has cardio protective effect against ISP-induced oxidative stress in rats.     

Caspase-12抑制剂对百草枯中毒大鼠肝损伤的保护作用

目的:观察caspase-12抑制剂Z-ATAD-FMK对百草枯染毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡的影响,以及通过血清SOD和MDA的检测,探讨其对百草枯中毒大鼠肝脏保护作用和对机体氧化应激反应的作用。方法:50只健康Wistar大鼠随机分三组:A组为正常对照组;B组为模型组(PQ染毒);C组抑制剂组(PQ/Z-ATAD-FMK),于3d、7d处死B组和C组各10只大鼠。取血检测ALT、TBIL、SOD和MDA;HE染色观察肝组织病理学变化;免疫组化法检测caspase-12蛋白;二苯胺法检测细胞凋亡率。SPSS18.0统计分析。结果:Z-ATAD-FMK抑制剂组ALT、TBIL、MDA值低于模型组(P0.05),SOD高于模型组(P0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P0.05);HE染色显示凋亡和坏死程度也较模型组轻。结论:Caspase-12抑制剂Z-ATAD-FMK能减少百草枯中毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对肝脏具有保护作用,同时可以抑制百草枯中毒大鼠的氧化应激反应。     

Hepatoprotective Effect of Manganese Chloride Against CCl4-Induced Liver Injury in Rats

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl₄)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl₄-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl₄ increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus, the histopathalogical studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl₄-induced oxidative liver damage.     

ConA引起小鼠肝损伤实验研究

目的探讨conA引起免疫性肝损伤机实验条件。方法测定两个浓度,不同时间点ConA尾静脉注射后小鼠转氨酶水平及肝、脾病理变化。结果15mg／kgConA尾静脉注射后8h,血清转氨酶升高,但病检无明显改变;20mg／kgConA尾静脉注射,脾指数6h达峰值,10h肝脏病理变化显著,转氨酶水平达峰值。结论20mg／kgConA小鼠尾静脉注射6h后脾病变达高峰,10h可引起显著性肝损害。