Decreased IgA+ plasma cells and IgA expression in acute liver necrosis mice

AIM: To investigate the number of intestinal immunoglobulin A (IgA+) plasma cells and expression of intestinal IgA in mice with acute liver necrosis. METHODS: A model of acute liver necrosis was established by intraperitoneal injection of galactosamine (GalN) and lipopolysaccharide (LPS). Sixty mice were randomly divided into one of 4 equal groups: normal control, acute liver necrosis, LPS, or GalN. Hematoxylin and eosin staining, immunohistochemistry, and an enzyme-linked immunosorbent assay were employed to assess liver and intestinal injury, count intestinal IgA+ plasma cells, and measure the expression level of IgA and interferon γ (IFN-γ) in the small intestinal mucosa of mice. RESULTS: Injured intestinal mucosa was observed in the acute liver necrosis group but not in the normal, LPS or GalN groups. Compared with the normal group,intestinal IgA+ plasma cells were slightly decreased in the LPS and GalN groups [429 ± 20 per high power f ield (HPF), 406 ± 18/HPF, respectively], whereas they were markedly decreased in the acute liver necrosis group (282 ± 17/HPF vs 495 ± 26/HPF in normal group, P < 0.05). The expression of intestinal IgA was also slightly decreased in LPS and GalN groups, but was markedly reduced in the acute liver necrosis group as determined by enzyme-linked immunosorbent assay (P < 0.05). In contrast, the level of IFN-γ was slightly increased in LPS, GalN and acute liver necrosis groups, but with no statistical signif icance (P > 0.05). CONCLUSION: Intestinal IgA+ plasma cells and IgA expression levels indicating that mucosal immune barrier dysfunction, does exist in acute liver necrosis.     

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.     

Enteral glutamine pretreatment does not decrease plasma endotoxin level induced by ischemia-reperfusion injury in rats

AIM： To investigate whether oral glutamine pretreatment prevents impairment of intestinal mucosal integrity during ischemia-reperfusion （I/R） in rats. METHODS： The study was performed as two series with 40 rats in each. Each series of animals was divided into four groups. The first group was used as a control. Animals in the second group were only pretreated with oral glutamine, 1 g/kg for 4 d. The third group received a normal diet, and underwent intestinal I/R, while the fourth group was pretreated with oral glutamine in the same way, and underwent intestinal I/R. Intestinal mucosal permeability to ^51Cr-labeled EDTA was measured in urine in the first series of animals. In the second series, histopathological changes in intestinal tissue and plasma endotoxin levels were evaluated. RESULTS： Intestinal I/R produced a significant increase in intestinal permeability, plasma endotoxin level and worsened histopathological alterations. After intestinal I/R, permeability was significantly lower in glutamine- treated rats compared to those which received a normal diet. However, no significant change was observed in plasma endotoxin levels or histopathological findings. CONCLUSION： Although glutamine pretreatment seems to be protective of intestinal integrity, upon I/R injury, such an effect was not observable in the histopathological changes or plasma endotoxin level.     

Protective effects of N-acetylcysteine on brain-dead rat liver

BACKGROUND: Brain-dead donors have been the main sources in organ transplantation. But many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine (NAC) on liver injury. METHODS: A total of 30 Wistar rats were randomized into 3 groups: normal control group (C), brain-dead group (B), and NAC pretreatment group (N). At 4 hours after the establishment of a brain-dead model, serum was collected to determine the levels of ALT, AST, TNF-αand hyaluronic acid (HA). Hepatic tissue was obtained for electron microscopic examination. RESULTS: At 4 hours, the levels of ALT, AST, TNF-a, and HA in group N were significantly higher than those in group C, but these parameters were significantly lower than those in group B. Electron microscopy showed activated Kupffer cells, denuded sinusoidal endothelial cells (SECs), and widened fenestration in group B, but eliminated activation of Kupffer cells and intact SECs in group N. CONCLUSION: Brain death can cause liver injury, and N-acetyleysteine can protect the liver from the injury.     

Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats

AIM： To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis （NASH） in rats. METHODS： Thirty-two Sprague-Dawley （SD） rats were randomly divided into control group and model group. Rats in the control group were given normal diet, and rats in the model group were given fat-rich diet. Eight rats in each group were killed at end of the 8th and 12th wk, respectively. The levels of endotoxin, D-xylose, TG, TC, ALT and AST, intestinal tissue SOD and MDA as well as intestinal mucus secretory IgA （sIgA） were measured. The pathology of liver was observed by HE staining. RESULTS： At end of the 8th wk, there was no marked difference in the levels of endotoxin, D-xylose and sIgA between the two groups. At end of the 12th wk, rats in the model group developed steatohepatitis and had a higher serum level of endotoxin （P = 0.01） and D-xylose （P = 0.00） and a lower serum level of sIgA （P = 0.007）. CONCLUSION： Intestinal mucosa barrier malfunction may exist in NASH rats and may be an important promoter of NASH in rats.     

Protective effect of selenium-enriched lactobacilluson CCI_4-induced liver injury in mice and its possible mechanisms

AIM: To study the protective effects and mechanisms of Se-enriched lactobacillus on liver injury caused by carbon tetrachloride(CCI_4) in mice. METHODS: Seventy-two ICR mice were randomly divided into four groups: normal group, CCl_4-induced model group, low Se-enriched lactobacillus treatment group(L-Se group), and high Se-enriched lactobacillus treatment group(H-Se group). During a 3-wk experimental period, the common complete diet was orally provided daily for normal group and model group, and the mice in L-Se and H-Se groups were given a diet with 2 and 4 mg of organoselenium from Se-enriched lactobacillus per kg feed, respectively. From the 2~(nd) wk of experiment, the model group, L-Se group, and H-Se group received abdominal cavity injection of olive oil solution containing 500 mL/L CCl_4(0.07 mL/100 g body mass) to induce liver injury, and the normal group was given olive oil on every other day for over 2 wk. In the first 2 wk post injection with CCl_4, mice in each group were killed. The specimens of blood, liver tissue, and macrophages in abdominal cavity fluid were taken. Then the activities of the following liver tissue injury-associated enzymes including glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), alanine aminotransferase(ALT) and aspartate aminotransferase(AST) as well as malondialdehyde(MDA) content were assayed. Changes of phagocytic rate and phagocytic index in macrophages were observed with Wright-Giemsa stain. Plasma TNF-α level was measured by radioimmunoassay. The level of intracellular free Ca~(2+)([Ca~(2+)]_i) in hepatocytes was detected under a laser scanning confocal microscope. RESULTS: During the entire experimental period, the AST and ALT activities in liver were greatly enhanced by CCl_4 and completely blunted by both low and high doses of Se-enriched lactobacillus. The Se-enriched lactobacillusprotected liver homogenate GSH-Px and SOD activities were higher or significantly higher than those in model group and were close to those in normal group. CCl_4 significantly increased MDA content in liver homogenates, while administration of Se-enriched lactobacillus prevented MDA elevation. Phagocytic rate and phagocytic index of macrophages decreased after CCl_4 treatment compared to those in normal control, but they were dramatically rescued by Se-enriched lactobacillus, showing a greatly higher phagocytic function compared to model group. CCl_4 could significantly elevate plasma TNF-α and hepatocyte[Ca~(2+)]_i level, which were also obviously prevented by Se-enriched lactobacillus. CONCLUSION: Se-enriched lactobacillus can intervene in CCl_4-induced liver injury in mice by enhancing macrophage function activity to keep normal and beneficial effects, elevating antioxidant-enzyme activities and reducing lipid peroxidation reaction, inhibiting excessive release of TNF-α, preventing the dramatic elevation of [Ca~(2+)]_i in hepatocytes.     

N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice

BACKGROUND:Toll-like receptor 2 and 4(TLR2/4)may play important roles in ischemia-reperfusion(I/R)injury, and N-acetylcysteine(NAC)can prevent the generation of reactive oxygen species(ROS)induced by I/R injury.This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS:BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group(SH),a hepatic ischemia/ reperfusion group(I/R)or a NAC pretreated,hepatic I/R group(I/R-NAC).The levels of TNF-αin the portal vein and plasma alanine aminotransferase(ALT)were measured at 1 and 3 hours after reperfusion.The lung wet-to-dry ratio was measured,and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS:Compared with the I/R group,the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05).The levels of portal vein TNF-αand plasma ALT increased continuously in the I/R group at 1 and 3 hours of reperfusion compared with the SH group;however,they declined significantly in the group pretreated with NAC (P<0.05).The extent of lung edema was relieved in the I/ R-NAC group compared with the I/R group(P<0.05).CONCLUSIONS:TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury.NAC inhibited the activation of TLR2/4 and the induction of TNF-α resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.     

Melatonin protects liver from intestine ischemia reperfusion injury in rats

AIM： To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats. METHODS： One hundred and fifty male Wistar rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin exposure group, alcohol solvent control group and normal saline control group. Rats in the melatonin exposure group received intraperitoneal （IP） melatonin （20 mg/kg） 30 min before intestinal ischemia-reperfusion （IR）, rats in the alcohol solvent control group received the same concentration and volume of alcohol, and rats in the normal saline control group received the same volume of normal saline. Serum samples were collected from each group 0.5, 1, 6, 12, and 24 h after intestinal IR. Levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured with an auto-biochemical analyzer. Serum TNF-α was tested by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA） in liver was detected by colorimetric assay. Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope. RESULTS： The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups （P 〈 0.05）. The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels （%） 6, 12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups （P 〈 0.05）. CONCLUSION： Exotic melatonin can inhibit the activity of ALT, AST and TNF-α, decrease the accumulation of MDA, and depress the expression of ICAM-1 in liver after intestinal IR injury, thus improving the liver function.     

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intraven ously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals. RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50 μg/kg pcDNA3-ALR DNA. The effect of intravenous injection of recombinant pcDNA3 ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid, the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P<0.01). CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level of AST and ALT in CCl4-intoxicated rats.     

疏肝祛瘀通络降浊法对大鼠非酒精性脂肪性肝炎的保护作用

目的探讨非酒精性脂肪性肝炎大鼠内毒素性肝损伤机制及中药对其影响。方法用喂饲高脂饮食的方法建立非酒精性脂肪性肝炎大鼠模型。4周后用疏肝祛瘀通络降浊法分小、中、大剂量进行治疗,12周后处死测定血脂、ALT、内毒素(ET)、肿瘤坏死因子(TNF-α)和白细胞介素(IL-1β)的含量;免疫组化法观察肝组织CD14和核转录因子(NF-κB)的表达;RT-PCR检测脂多糖结合蛋白(LBP)和4型Toll样受体(TLR-4)mRNA的表达。同期正常饮食饲养大鼠作对照。结果第12周时,模型组大鼠腹主动脉血清内毒素水平较正常组明显升高,有显著性差异;中剂量治疗组大鼠血清ET、TNF-α、IL-1β水平明显低于模型组,差异有显著意义。模型组大鼠肝组织CD14阳性细胞数量明显增多,主要分布于肝窦内,部分呈灶型聚集;与模型组相比,中剂量治疗组大鼠肝组织CD14阳性细胞数量明显减少。模型组可见少量细胞核染色的NF-κB阳性细胞散在分布于汇管区。模型组肝组织LBPmRNA和TLR-4mRNA表达均明显上调,与正常组比较差异均有显著意义;中剂量治疗组大鼠肝组织LBPmRNA和TLR-4mRNA表达均较模型组明显下调,且有显著性差异。结论疏肝祛瘀通络降浊法对非酒精性脂肪肝有疗效,可能与其降低血清内毒素水平和下调肝组织内毒素相关受体表达继而减轻炎症性肝损害有关。     

枳黄方对急性酒精性肝损伤大鼠内毒素信号转导通路中白细胞分化抗原14的影响

[目的]探讨酒精性肝损伤时，枳黄方对内毒素信号通路中白细胞分化抗原14（CD14）表达的影响。[方法]将75只Wistar大鼠随机分为空白对照（正常）组、酒精攻击（模型）组、枳黄方（治疗）组，10d后，处死大鼠，取大鼠血清和肝脏测定丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST），苏木精-伊红染色观察肝脏病理变化，基质染色法测定血清内毒素，免疫组化法测定肝脏肿瘤坏死因子α（TNF-α），RT—PCR法测定肝组织CD14mRNA的变化。[结果]治疗组肝脏病理表现较模型组好，其血清内毒素、ALT、AST和肝组织TNF-α、CD14mRNA表达水平均高于正常组（P〈0．05，〈0．01，〈0．01，〈0．01，〈0．05），且均显著低于模型组（均P〈0．01）。[结论]枳黄方能显著降低内毒素信号转导通路上CD14基因水平的表达，减少肝组织TNF-α的表达，这可能是其对大鼠酒精性肝损伤有较明显保护作用的机制之一。     

Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138

AIM: To investigate the possible use of the multiple cytokine production modulator, Y-40138, as a novel immunotherapy in the rat nonalcoholic steatohepatitis(NASH) model.METHODS: We allocated 6-wk-old male F344 rats to choline-supplemented, L-amino acid-defined (CSAA) diet (control group), CSAA diet + Y-40138 (control +Y-40138 group), choline-deficient, L-amino acid-defined (CDAA) diet (NASH group), or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group, we measured the plasma alanine aminotransferase (ALT) levels, and the plasma and liver levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-10 (IL-10). Tissue specimens of phosphate buffered saline-perfused liver were subjected to hematoxylin and eosin staining, Azan staining, Sirius red staining, and immunohistochemical staining (for Kupffer cells and TNF-α). We then extracted Kupffer cells from the collagenase-perfused livers using the Percoll gradient centrifugation method, and measured the TNF-α levels in the supernatant ( in vitro TNF-α production by Kupffer cells) using an enzyme-linked immunosorbent assay kit. RESULTS: In comparison to the NASH group, serum ALT elevation was mild, production of serum and liver TNF-α and IFN-γ was inhibited, and IL-10 production was increased in the NASH + Y-40138 group. Amelioration of liver histology was also noted in the NASH + Y-40138 group. Kupffer cell immunohistochemical staining revealed no differences between groups, whereas TNF-α immunohistochemical staining showed fewer stained cells in the NASH + Y-40138 group than in the NASH group. The TNF-α levels in the in-vitro Kupffer cell culture supernatant were lower in the NASH + Y-40138 group than in the NASH group.CONCLUSION: Administration of Y-40138 to NASH model rats reduced hepatic inflammation and suppressed fibrosis. These results indicate that the multiple cytokine production modulator, Y-40138, is promising as a novel treatment for NASH.     

Preventive effect of cyclosporin A on experimentally induced acute liver injury in rats

Abstract: We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat-killed Propionibacterium acnes (P. acnes) and subsequent injection of lipopolysaccharide (LPS). Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor-α (TNF-α) production, without changing the TNF-α mRNA level in the liver, and plasma interferon-γ (IFN-γ), following LPS injection in this model. Twenty-four-hour mortality was also markedly improved, from 100% in the P. acnes plus LPS group to 0% in the CsA-pretreated group. Although direct addition of CsA to isolated hepatic macrophages from P. acnes-pretreated rats did not prevent the production of TNF-α and active oxygen species, isolated hepatic macrophages from P. acnes plus CsA-pretreated rats significantly reduced their production in response to the addition of LPS. These results suggest that CsA protects against P. acnes plus LPS-induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN-γ levels.     

NALP3炎性体在小鼠非酒精性脂肪性肝炎发病中的作用

目的 探讨NALP3炎性体在非酒精性脂肪性肝炎(NASH)小鼠发病中的作用.方法 予C57BL小鼠高脂饮食(高脂组)及脂多糖建立非酒精性脂肪肝模型(NASH组),同时设立正常饮食组作为对照.观察各组小鼠血清ALT、AST值与计算肝指数,评定脂肪性肝炎程度,ELISA法测定肝脏TNF-α水平,蛋白质印迹法测定NF-κB、NALP3、caspase-1、ASC的表达;实时荧光定量反转录-PCR检测NALP3、caspase-1、ASC mRNA的表达水平.数据处理采用单因素方差分析及LSD法.结果 NASH组小鼠ALT、AST及肝指数明显高于高脂组,差异有统计学意义(P＜0.05),高脂组和NASH组的NALP3 mRNA表达高于正常对照组(P＜0.05).NASH组caspase-1和ASC mRNA表达水平明显高于正常对照组及高脂组(P＜0.01),高脂组caspase-1和ASC mRNA表达高于正常对照组(P＜0.05).NASH组NALP3、caspase-1和ASC表达水平明显高于正常对照组(P＜0.01),NASH组NALP3、caspase-1和ASC表达水平明显高于高脂组(P＜0.05),高脂组NALP3、caspase-1和A SC表达水平与正常对照组无明显差异(P＞0.05).结论 NALP3炎性体参与胰岛素抵抗的形成,可能是影响NASH发生和发展的重要因素.     

Choline Deficiency Augments and Antibody to Tumor Necrosis Factor-α Attenuates endotoxin-Induced Hepatic Injury

Alcoholic liver disease can be associated with hepatic choline deficiency and hepatic steatosis, abnormalities also observed in rats administered choline-deficient (CD) diets. Bacterial lipopolysaccharides (LPS) have been postulated to play a key role in this choline deficiency model of liver injury, and LPS hepatotoxicity is mediated to a major extent by the inflammatory cytokine tumor necrosis factor-α (TNF-α). This study addressed the following questions: Does LPS administration exacerbate an in vivo liver injury induced by choline deficiency? If so, do CD rats have increased serum TNF-α concentrations and does pretreatment anti-TNF-α IgG attenuate this injury? Rats administered choline-sufficient (CS) or CD diets for 16 days were intravenously administered either saline or LPS. One group of CD rats also received a single dose of anti-TNF-α IgG before LPS administration. Changes in histology and serum transaminase levels were determined. Both liver histology and serum transaminases were unchanged in the CS group treated with LPS, compared with the CS group treated with saline (control group). However, compared with this control group, transaminases were 5- to 7-fold higher in saline-treated CD rats and 30- to 50-fold higher in LPS-treated CD rats. Livers of saline-treated CD rats had massive fatty infiltration, and no necrosis but livers of LPS-treated CD rats showed both extensive fatty infiltration and large areas of necrosis. Serum TNF-α concentrations in CD rats (saline or LPS treated) were significantly elevated, compared with levels in corresponding CS rats. Pretreatment with the anti-TNF-α IgG prevented hepatonecrosis in LPS-treated CD rats and lowered their serum transaminases by one-third. Thus, LPS administration exacerbated liver injury induced by choline deficiency, and this injury was probably partially mediated by TNF-α and attenuated by anti-TNF-α IgG.     

HSP70、IL-6和TNF—OL在CCl4诱导的小鼠急性肝损伤组织中的表达及意义

目的探讨HSP70、IL-6和TNF—α在急性肝损伤及再生过程中的作用机制。方法将100只雄性小鼠分为观察组90只和对照组10只。观察组腹腔注射CCl4制作急性肝损伤模型,制模后3、6、12、24、30、36、42、48、54h各处死10只。赖氏法检测两组血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平的变化;HE染色法观察小鼠肝脏组织病理变化;Westernblot法检测肝损伤过程中热休克蛋白70（HSP70）、IL-6和TNF-α蛋白表达及变化趋势。结果与对照组相比,观察组血清ALT、AST逐渐升高,36h达到高峰,后逐渐减低;肝脏失去正常结构,36h时最为显著,后逐渐减轻;与对照组相比,肝脏HSP70、IL-6和TNF-α蛋白的表达呈以下趋势：HSP70在3、6、12h先升高,12h至最高,24h时降低,30h至最低点,后再升高;IL-6在3、6、12h逐渐减低,24h时升高,30h至最高点,后又逐渐减低,54h时仍略高于正常水平;TNF—α先逐渐升高,30h达到高峰,后又逐渐降低,但明显高于正常水平。结论HSP70、IL-6和TNF—α在小鼠急性肝损伤以及肝再生过程中变化明显,可能与急性肝损伤的发生、发展密切相关。     

鲜生地对肝损伤模型大鼠枯否细胞功能的影响

目的探讨鲜生地在大鼠肝损伤时对肝脏枯否细胞功能的影响。方法取健康成年大鼠64只,随机分成4组:假手术组,肝损伤组,肝损伤+鲜生地组和肝损伤+乳果糖组。前两组以生理盐水灌胃,后两组分别以鲜生地和乳果糖灌胃。观察大鼠血浆内毒素(ET)、肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、谷丙转氨酶(ALT)以及枯否细胞表面CD68蛋白表达。结果与肝损伤组比较,鲜生地组和乳果糖组血浆ET、TNF-α、IL-1、ALT明显降低(P<0.05),CD68蛋白表达减少。结论鲜生地具有抑制肝脏枯否细胞吞噬及分泌作用,减少炎症因子释放,从而减轻肝细胞损伤。     

降脂平肝汤对非酒精性脂肪性肝病大鼠肠源性内毒素血症的影响

目的：观察复方中药降脂平肝汤对非酒精性脂肪性肝病（nonalcoholic fatty liver disease，NAFLD）大鼠肠源性内毒素血症（intestinal endotoxemia，IETM）的影响，探讨其作用机制。方法：21只Wistar大鼠随机分为正常组、模型组和中药治疗组。除正常组大鼠饲以普通饲料外，其余两组采用富含高不饱和脂肪酸的高脂饮食16周复制大鼠NAFLD模型，中药治疗组同时以复方中药降脂平肝汤混悬液灌胃。观察动物一般情况，计算肝指数、肝组织细胞脂变及炎症活动程度，检测肝组织Tch、TG、血清ALT、血浆肿瘤坏死因子α（Tumor Necrosis Factor-α，TNFα）和内毒素（Endotoxin，ET）含量等指标。结果：降脂平肝汤明显改善了NAFLD大鼠的肝指数、肝组织脂肪变程度、炎症活动程度，中药治疗组大鼠肝组织Tch与TG含量、血浆ALT活性与TNFα、ET含量均比模型组显著降低（P〈0．05，P〈0．01）。结论：降脂平肝汤减轻IETM，调节脂质代谢是其防治NAFLD的重要机制。     

模拟失重对大鼠实验性胃溃疡氧化应激状态的影响

目的探讨模拟失重对乙酸诱导的大鼠实验性胃溃疡氧化应激状态的影响及可能机制。方法 32只SD大鼠随机分为4组,即尾部悬吊7 d组、尾部悬吊14 d组和相应的同步对照组。采用乙酸烧灼法制备大鼠慢性胃溃疡模型,造模后第3天悬吊组大鼠采用尾悬吊法建立模拟失重动物模型。游标卡尺检测胃溃疡面积,生化比色法测定大鼠血清中丙二醛(MDA)含量,超氧化物岐化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性。结果与对照7 d组相比,悬吊7 d组大鼠溃疡面积显著增大(t=5.661,P<0.01);与对照14 d组比较,悬吊14 d组溃疡面积显著增大(t=4.233,P<0.01),血清MDA含量及SOD活性显著增高(t=2.641,P<0.05,t=5.758,P<0.01);与悬吊7 d组比较,悬吊14 d组溃疡面积显著减小(t=3.805,P<0.01),血清MDA含量及SOD活性显著增高。血清GSH-PX活性差异无统计学意义(P<0.05)。结论模拟失重可加重溃疡氧化应激反应,延迟溃疡愈合。