Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway

The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1–TLRs–NF-κB signaling pathway.     

NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis

Interleukin-33 (IL-33) is thought to be released during cellular death as an alarming cytokine during the acute phase of disease, but its regulation in vivo is poorly understood. We investigated the expression of IL-33 in two mouse models of acute hepatitis by administering either carbon tetrachloride (CCl(4) ) or concanavalin A (ConA). IL-33 was overexpressed in both models but with a stronger induction in ConA-induced hepatitis. IL-33 was weakly expressed in vascular and sinusoidal endothelial cells from normal liver and was clearly induced in CCl(4) -treated mice. Surprisingly, we found that hepatocytes strongly expressed IL-33 exclusively in the ConA model. CD1d knock-out mice, which are deficient in NKT cells and resistant to ConA-induced hepatitis, no longer expressed IL-33 in hepatocytes following ConA administration. Interestingly, invariant NKT (iNKT) cells adoptively transferred into ConA-treated CD1d KO mouse restored IL-33 expression in hepatocytes. This strongly suggests that NKT cells are responsible for the induction of IL-33 in hepatocytes.     

High mobility group box chromosomal protein 1 in acute-on-chronic liver failure patients and mice with ConA-induced acute liver injury

High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in many inflammatory disorders, but little is known about its role in acute-on-chronic liver failure (ACLF). Here, we investigated the relationship between the expression of HMGB1 and the disease onset and severity of ACLF patients and mice with acute liver injury/failure induced by concanavalin A (ConA). Peripheral blood mononuclear cells (PBMCs) and serum from ACLF patients were collected, and a mouse model of acute liver injury/failure was induced by ConA. HMGB1 mRNA expression in patient PBMCs or in murine livers and serum HMGB1 protein in ACLF patients and mice were assayed by RT-PCR and Western blotting, respectively. HMGB1 translocation in hepatocytes of ConA-treated mice was assessed by immunohistochemical staining. Up-regulated HMGB1 mRNA levels in PBMCs and accumulated protein in serum were both correlated with disease severity in ACLF patients. In the animal model, HMGB1 levels increased at 4 h and reached its peak value at 8-12 h after challenge with ConA, which suggests that HMGB1 is a relatively late proinflammatory cytokine compared with TNF-α. Translocation of HMGB1 from the nucleus to the cytoplasm in hepatocytes was correlated with the severity of liver injury in mice. While specific anti-HMGB1 antibodies and nicotine protected mice from acute liver injury/failure by reducing mortality and improving liver tissue injury, treatment with recombinant HMGB1 led to an increased mortality due to ConA challenge. Thus, the data from the present study suggest that HMGB1 plays a critical role in the systemic inflammation of ACLF and could be a potential therapeutic target in the treatment of ACLF.     

凋亡相关分子的表达上调在免疫性肝损伤中的作用探讨

检测刀豆蛋白A(concanavalin A,ConA)诱导的小鼠急性肝损伤模型中凋亡相关分子的表达,并探讨其意义。以小鼠尾静脉注射15 mg/kg ConA建立急性肝损伤模型;AnnexinⅤ染色检测肝细胞的凋亡率;流式细胞术检测不同时间点肝细胞表面凋亡受体Fas、DR5的表达,以及肝浸润淋巴细胞表面凋亡配体FasL、TRAIL的表达。结果显示,与正常小鼠肝细胞凋亡率3.36%±0.69%相比,ConA诱导小鼠急性肝损伤后肝细胞的凋亡率显著上升,12 h为13.52%±0.68%,24 h达20.92%±0.66%。同时,肝细胞表面Fas、DR5的表达明显上升,肝浸润淋巴细胞表面FasL、TRAIL亦呈显著上调表达。结果表明,在ConA诱导的急性肝损伤发生发展过程中,肝细胞表面凋亡相关分子Fas、DR5与肝浸润淋巴细胞表面凋亡配体FasL、TRAIL的表达上调以及相互作用是导致肝损伤的重要因素。     

NCPP treatment alleviates ConA-induced hepatitis via reducing CD4+T activation and NO production

Corynebacterium parvum (CP), a kind of immunomodulator, has been well documented in many diseases. Non-cell C. parvum product (NCPP) is a newly-found nano-preparation. To investigate the effect of NCPP on Con A-induced murine severe hepatitis, we pretreated mice with NCPP intraperitoneally. After 12 h, ConA (25 μg/g body wt) was injected intravenously to provoke severe hepatitis and the degree of liver injury was evaluated by serum transaminase analysis and heptatic tissue pathology. Results have shown that levels of serum transaminase and degree of liver injury in ConA/NCPP groups had significantly declined than those in ConA/PBS groups. Notably, results of flow cytometry have demonstrated that activation of CD4+T cells in ConA/NCPP groups has been down-regulated, compared with ConA/PBS groups. Further, levels of serum and KC-related nitric oxide (NO) was displayed significantly lower in ConA/NCPP groups than those in ConA/PBS groups. The results indicate that NCPP may alleviate ConA-induced hepatitis by reducing CD4+T activation and NO production.     

Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice

Objective

We investigated whether dexmedetomidine provided protective effects on cecal ligation and puncture (CLP)–induced septic mice, through suppressing the expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6)] and high mobility group box 1 (HMGB1).

Methods

The model of sepsis was set up by CLP in 136 male BALB/c mice (40 mice for survival studies and 96 for cytokine studies) which were divided into four groups, including a C, CLP, DEX + CLP and CLP + DEX group. The serum levels of TNF-α, IL-6 and HMGB1 were detected at 6, 12, 24 and 48 h after operations, and lung HMGB1 mRNA were analyzed at 24 and 48 h. The mortality rates were calculated 7 days after the operations.

Results

The mortality rates 7 days after operations were significantly lower in the CLP + DEX (50 %) and DEX + CLP (30 %) groups than in the CLP group (90 %). Serum concentrations of IL-6 and TNF-α decreased significantly in dexmedetomidine administration groups compared with the CLP group. The levels of HMGB1 and lung HMGB1 mRNA were lower in the dexmedetomidine administration groups than in the CLP group. There was a significant correlation between lung HMGB1 mRNA and serum HMGB1(r = 0.858).

Conclusions

Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.     

NOD2: a potential target for regulating liver injury

The recent discovery of bacterial receptors such as NOD2 that contribute to crosstalk between innate and adaptive immune systems in the digestive tract constitutes an important challenge in our understanding of liver injury mechanisms. The present study focuses on NOD2 functions during liver injury. NOD2, TNF-alpha and IFN-gamma mRNA were quantified using real-time PCR in liver samples from patients and mice with liver injury. We evaluated the susceptibility of concanavalin A (ConA) challenge in NOD2-deficient mice (Nod2-/-) compared to wild-type littermates. We tested the effect of muramyl dipeptide (MDP), the specific activator of NOD2, on ConA-induced liver injury in C57BL/6 mice. We studied the cellular distribution and the role of NOD2 in immune cells and hepatocytes. We demonstrated that NOD2, TNF-alpha and IFN-gamma were upregulated during liver injury in mice and humans. Nod2-/- mice were resistant to ConA-induced hepatitis compared to their wild-type littermates, through reduced IFN-gamma production by immune cells. Conversely, administration of MDP exacerbated ConA-induced liver injury. MDP was a strong inducer of IFN-gamma in freshly isolated human PBMC, splenocytes and hepatocytes. Our study supports the hypothesis that NOD2 contributes to liver injury via a regulatory mechanism affecting immune cells infiltrating the liver and hepatocytes. Taken together, our results indicate that NOD2 may represent a new therapeutic target in liver diseases.     

CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice

Membrane microdomains consisting of sphingomyelin (SM) and cholesterol appear to be important for signal transduction in T-cell activation. The present study was designed to elucidate the role of membrane SM in vivo and in vitro using sphingomyelin synthase 1 (SMS1) knock out (SMS1(-/-)) mice and Concanavalin A (ConA)-induced hepatitis. After establishing SMS1(-/-) mice, we investigated CD4+ T-cell functions including proliferation, cytokine production and signal transduction in vivo. We also examined severity of hepatitis, cytokine production in serum and liver after ConA injection at a dose of 20 mg kg(-1). CD4+ T cells from SMS1(-/-) mice showed severe deficiency of membrane SM and several profound defects compared with wild-type controls as follows: (i) cellular proliferation and production of IL-2 and IFN-γ by co-cross-linking of CD3 and CD4; (ii) tyrosine phosphorylation of LAT and its association with ZAP-70; (iii) clustering and co-localization of TCR with lipid rafts. Consistent with these impaired CD4+ T-cell functions in vitro, SMS1(-/-) mice showed decreased serum levels of IL-6 and IFN-γ by ConA injection, which renders SMS1(-/-) mice less sensitive to ConA-induced hepatitis. These results indicated that the deficiency of membrane SM caused the CD4+ T-cell dysfunction through impaired lipid raft function contributed to protection of ConA-induced liver injury, suggesting that the membrane SM is critical for full T-cell activation both in vitro and in vivo.     

Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice

Using hepatitis B virus (HBV) transgenic mice as recipients of virus-specific cytotoxic T lymphocytes (CTLs), we recently showed that polymorphonuclear neutrophils (PMNs) and the matrix-degrading metalloproteinases (MMPs) they produce are necessary for the intrahepatic recruitment of antigen nonspecific mononuclear cells that amplify the liver damage initiated by the CTLs. We now report that the high-mobility group box 1 protein (HMGB1) is also involved in this process. Transfer of CTLs in HBV transgenic mice induces the translocation of HMGB1 from the nucleus to the cytoplasm of hepatocytes surrounding CTL-containing necroinflammatory liver foci, without significant net synthesis of HMGB1. Treatment of CTL-injected HBV transgenic mice with either recombinant Box-A or glycyrrhizin, two functional inhibitors of extracellular HMGB1, significantly decreases the intrahepatic recruitment of PMNs and all other inflammatory cells, in the face of intact homing of virus-specific CTLs into the liver. The inhibition of PMN chemoattraction explains the mode of action of glycyrrhizin, which has long been used in Japan for the treatment of hepatitis, and suggests that new and more potent inhibitors of HMGB1 may be useful for the treatment of patients chronically infected with HBV.     

Curcumin inhibits placental inflammation to ameliorate LPS-induced adverse pregnancy outcomes in mice via upregulation of phosphorylated Akt

Introduction

Excessive inflammation results in adverse pregnancy outcomes, including embryonic resorption, fetal growth restriction, and preeclampsia. This study investigated whether curcumin, a highly safe anti-inflammation drug, had protective effect on lipopolysaccharide (LPS)-treated pregnant mice.

Method

A mouse model of LPS-induced adverse pregnancy outcomes was generated by daily administering LPS from GD 13.5 to GD 16.5. Curcumin was given from GD 0.5. The effects of curcumin on maternal hypertension, proteinuria, pregnancy outcomes, as well as proinflammatory factors, chemokines, Akt, JNK, and P38 levels in placenta were examined.

Results

Systolic blood pressure (156.6 ± 5.056 versus 125.5 ± 3.617 mmHg; P < 0.05) and proteinuria (22.36 ± 2.22 versus 12.70 ± 1.04 mg/L; P < 0.05) were decreased in the LPS+curcumin-treated group, as compared with the LPS-treated group. Curcumin also increased the number of live pups, fetal weight, and placental weight, while it decreased fetal resorption rate. Moreover, increased placental TNF-α, IL-1β, and IL-6 expressions in LPS-treated group were significantly suppressed after curcumin administration. Furthermore, decreased p-Akt level in placenta induced by LPS was improved by curcumin. Of note, the expression of p-Akt increased by curcumin was accompanied by the decreased chemokines MCP-1 and MIP-1 levels and fewer CD68-positive macrophages in the placenta.

Conclusion

Curcumin inhibited the expression of proinflammatory factors and macrophage infiltration in placenta and ameliorated LPS-induced adverse pregnancy outcomes in mice by inhibiting inflammation via upregulation of phosphorylated Akt.

     

High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as an early endogenous alarmin of inflammation following injury and as a late mediator of lethality in sepsis. Although HMGB1 has been implicated in acute lung injury, rheumatoid arthritis, and allograft rejection, its role in T-cell mediated hepatitis remains obscure. Here, we investigated the role and the underlying mechanisms of HMGB1 in concanavalin A (Con A) induced hepatic injury. We demonstrate that high levels of HMGB1 were detected in the necrotic area and in the cytoplasm of hepatocytes after Con A treatment. Administration of exogenous recombinant HMGB1 enhanced Con A-induced hepatitis, while blockade of HMGB1 protected animals from T cell-mediated hepatitis as evidenced by decreased serum transaminase, associated with reduced hepatic necrosis and mortality. Blockade of HMGB1 by a neutralizing antibody inhibited proinflammatory cytokine production, NFκB activity, and the late stage of T/NKT cell activation. These finding thus suggest a pivotal factor of HMGB1 in Con A-induced hepatitis. Blockage of extracellular HMGB1 may represent a novel therapeutic strategy to prevent hepatic injury in T cell-mediated hepatitis.     

The pentapeptide PLNPK inhibits systemic lupus erythematosus-associated renal damage

Objective

This study aimed to observe the therapeutic effect of pentapeptide PLNPK on systemic lupus erythematosus (SLE) in mice, and to study the inhibitory effect of PLNPK on activation of T cells in vivo.

Methods

Murine SLE-like chronic graft-versus-host disease (cGVHD) was induced. After treatment with PLNPK (100, 200, 400 μg/kg per day) for 70 days, serum blood urea nitrogen, creatine, total cholesterol, triglyeride and albumin were tested, and serum levels of anti-dsDNA and anti-histone antibodies were detected by ELISA. The pathological damage and IgG deposition in the kidney were identified. Concanavalin A (ConA)-induced T lymphocyte proliferation in SLE mice was also tested.

Results

PLNPK can reduce serum blood urea nitrogen, creatine, total cholesterol, triglyeride, and elevate serum albumin, and reduce levels of anti-dsDNA and anti-histone antibodies in the murine SLE model. Pathological damage and IgG deposition in the kidney were reduced in the PLNPK-treated group. PLNPK inhibited T lymphocyte infiltration in kidney tissues and ConA-induced T lymphocyte proliferation in SLE mice.

Conclusion

Our results demonstrate that PLNPK can suppress T cell function and reduce the production of autoantibodies, and may be a feasible and effective therapy in the SLE model.     

Modulation of intracellular machinery by beta-glycolipids is associated with alteration of NKT lipid rafts and amelioration of concanavalin-induced hepatitis

The integrity of lipid rafts in cell membranes is important for signal transduction. AIM: To determine the distinct effects of beta-glycolipids on the composition of lipid rafts in natural killer T (NKT) cells and on the level of expression of flotillin-2, leukocyte-specific protein tyrosine kinase (Lck), and STAT1-associated pathways. METHODS: The effects of glycolipids were determined by composition analysis of the raft domains, FACS analysis of the distribution patterns for the raft ganglioside, GM1, and fluorescence microscopy of raft patching. To evaluate the effects of the immune environment on glycolipid-associated alteration of lipid rafts, hepatitis was induced by an intravenous injection of concanavalin A (ConA) in mice treated with various glycolipids. RESULTS: The administration of beta-glucosylceramide, beta-lactosylceramide, and a combination of both significantly altered GM1 content in lymphocyte membranes in an environment-dependent manner. These effects were associated with altered expression levels of flotillin-2, Lck, and STAT1, and with a significant decrease in intrahepatic CD8+ lymphocyte trapping and the alleviation of ConA-induced hepatitis. The administration of alpha-glycolipids failed to induce similar effects. CONCLUSIONS: The alteration in the expression levels of flotillin-2, Lck, and STAT1 that occurs concomitantly with changes in lipid raft composition and structure following the administration of beta-glycolipids in ConA-induced hepatitis is microenvironment-dependent and is associated with decreased intrahepatic CD8(+) T lymphocyte trapping and amelioration of immune-mediated hepatitis.     

Analysis of the Gene Expression Profile of Curcumin-Treated Kidney on Endotoxin-Induced Renal Inflammation

Acute or chronic kidney inflammation is closely related to the progress of kidney diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The present study aimed to investigate the effects and explore the protective mechanism of curcumin on lipopolysaccharide (LPS)-induced kidney inflammation in mice using gene chip and pathological technology. Nine SPF Kunming mice (aged 6–8 weeks, weighing 20–25 g) were divided into three groups. Saline and LPS were injected intraperitoneally in a normal control group and a model group, respectively. Mice in the treatment group were first injected with curcumin (5 mg/kg) for 3 days before being injected with LPS (5 mg/kg). Kidney tissues were harvested at 6 h after treatment. Parts of kidney were fixed with 10 % formaldehyde for HE, Periodic acid-Schiff staining, and immunohistochemistry. Affymetrix gene chips (mouse 430 chip) were used to detect the renal gene expression profile, and the results were analyzed using bioinformatics methods. The renal gene expression profile showed that there are 148 Affy IDs (up-down group) whose levels of gene expression were increased after LPS stimulation and decreased by curcumin treatment and that there are 133 Affy IDs (down-up group) exhibiting the opposite trend. In the differentially expressed genes of the up-down group, 21 Gene Ontology (GO) genes were selected by screening function (P?≤?0.01). In the biological processes, most of the genes were found to be related to the genes of regulation of macrophage activation and macrophage activation-associated genes. In the cellular localization, there were four functional GO genes (P?≤?0.01); in the molecular structure, there were seven functional GO genes (P?≤?0.01). In the down-up group, there were functional GO genes (P?≤?0.01) and one functional GO gene (P?≤?0.01) in the biological process and the cellular localization, respectively. Macrophage infiltration could be observed as early as 6 h after LPS stimulation. Pretreatment with 5 mg/kg of curcumin significantly decreased the macrophage infiltration. At 6 h after LPS injection, significant decreased expression of M6PRBP-1 and NEDD-4 was observed in renal tissue. On the other hand, pretreatment with curcumin significantly increased renal M6PRBP-1 and NEDD-4 expression. In this study, we also found the signaling pathway and the possible target gene of the protective effects of curcumin on endotoxin-induced renal inflammation. The kidney gene expression profile in the inflammatory state was clarified by using gene chip technology. Furthermore, we confirmed that curcumin treatment can change the gene expression profile.     

Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.     

Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.     

Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression

High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of HMGB1 in a rat model of LPS-induced ALI. Rats underwent intraperitoneal injection of LPS to mimic sepsis-induced ALI. Propofol bolus (1, 5, or 10 mg/kg) was infused continuously 30 min after LPS administration, followed by infusion at 5 mg/(kg?·?h) through the left femoral vein cannula. LPS increased wet to dry weight ratio and myeloperoxidase activity in lung tissues and caused the elevation of total protein and cells, neutrophils, macrophages, and neutrophils in bronchoalveolar lavage fluid (BALF). Moreover, HMGB1 and other cytokine levels were increased in BALF and lung tissues and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. Propofol inhibited all the above effects. It also inhibited LPS-induced toll-like receptor (TLR)2/4 protein upexpression and NF-κB activation in lung tissues and human alveolar epithelial cells. Propofol protects rats and human alveolar epithelial cells against HMGB1 expression in a rat model of LPS-induced ALI. These effects may partially result from reductions in TLR2/4 and NF-κB activation.     

EGCG对ConA诱导的肝损伤小鼠NF-κB和ICAM-1表达的影响

目的通过观察表没食：于儿茶素没食子酸酯（EGCG）对ConA诱导的急性肝损伤小鼠肝组织中NF-κB及ICAM-1表达的影响,来探讨EGCG对小鼠的肝保护机制。方法C57BL／6小鼠分成4组：对照组、EGCG对照组、ConA模型组．EGCG＋ConA组。EGCG对照组及EGCG＋ConA组小鼠给予EGCGEl服（5mg／kg）10d后,予模型组小鼠静脉注射ConA（15mg／kg）建造肝损伤模型。采血及留取肝组织,HE法检测肝组织病理变化,ELISA法检测NF-KB及ICAM-1的表达。结果ConA模型组小鼠肝损伤明显,NF-κB及ICAM-1的表达明显增多,与对照组比较有显著性差异（P〈0．05）;EGCG治疗组肝损伤减轻且伴NF-KB及ICAM-1的表达下降,与模型组比较差异明显（P〈0．05）。结论EGCG对ConA诱导的免疫性肝损伤小鼠有保护作用．其机制可能与调节NF-κB及ICAM-1的表达有关。     

Sleep during concanavalin-A-induced hepatitis and peritonitis in inbred mice

STUDY OBJECTIVES: To assess the suitability of concanavalin-A-induced hepatitis as a model for investigating the relationships between hepatic disease and alterations in somnolence. DESIGN: We characterized the sleep patterns of various strains of inbred mice undergoing ConA-induced inflammation. SETTING: Southern Illinois University School of Medicine, Springfield, IL. Intervention: Intravenous or intraperitoneal administration of concanavalin-A. PARTICIPANTS: Inbred mice. MEASUREMENTS AND RESULTS: Intravenous and intraperitoneal administration of concanavalin-A both elicited strain-dependent changes in slow-wave sleep. ConA treatment also reduced spontaneous locomotor activity. ConA-induced changes in slow-wave sleep varied with dose, route of administration, and circadian period of administration. As compared with the other strains, C57BL/6J mice had lower serum concentrations of interferon-gamma at 8 hours after ConA administration. CONCLUSIONS: These data provide the first demonstration that sleep enhancement and reduced locomotor activity accompany hepatic inflammation in mice.