Effect of <Emphasis Type="Italic">N</Emphasis>-Acetylcysteine on Lipopolysaccharide-Induced Uveitis in Rats

Purpose In this study we investigated the in vivo effect of N-acetylcysteine (NAC) on lipopolysaccharide (LPS)-induced uveitis in rats. Methods To induce uveitis, LPS (100 μg) was injected into subcutaneous tissue of Wistar rats (170–190 g). NAC was injected intraperitoneally. Intracameral levels of protein, cells, nitrite, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined by spectrophotometry, hemocytometry, and enzyme-linked immunosorbent assay. Expression of TNF-α, IL-6, endothelial leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) mRNA was examined by real-time polymerase chain reaction. Results LPS injection elevated intracameral protein and cells, and the elevation was inhibited by NAC. LPS injection induced expression of TNF-α, IL-6, E-selectin, and ICAM-1 mRNA in the iris/ciliary body at 3 h, and iNOS mRNA at 6 h. The LPS-induced elevation of the mRNA levels was inhibited by NAC. NAC inhibited LPS-induced intracameral elevation of TNF-α, IL-6, and nitrite. Conclusion NAC decreased LPS-induced uveitis in vivo by reducing the expression of proinflammatory cytokines and adhesion molecules. Jpn J Ophthalmol 2007;51:14–20 ? Japanese Ophthalmological Society 2007     

Protective role of heme oxygenase-1 against endotoxin-induced uveitis in rats

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation. Cytokines, chemokines, and nitric oxide (NO) have been reported to play important roles. We have determined whether heme oxygenase (HO)-1, a heat shock protein, can suppress EIU. EIU was induced by a footpad injection of lipopolysaccharide (LPS) in male Lewis rats. Hemin, an inducer of HO-1, was injected intraperitoneally 1 hr prior to the LPS injection. HO-1 and HO-2 expression in the iris-ciliary body (ICB) was studied by real time PCR and Western blot analysis. The number of infiltrating cells and the protein concentration in the aqueous humor (AqH) were evaluated by microscopy and by protein assay. The expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta mRNA was determined by real time PCR. The concentration of nitrate plus nitrite, and levels of IL-6 and TNF-alpha in the AqH were also evaluated by Griess reagents and by enzyme-linked immunosorbent assay, respectively. The expression of HO-1 mRNA and protein, induced by LPS, was enhanced significantly by pre-injection of hemin (P<0.001). HO-2 was constitutively present in the ICB and was not up-regulated by LPS or by hemin. The number of infiltrating cells and the concentration of protein in the AqH was significantly elevated by LPS injection, and hemin significantly reduced the number of cells and the protein concentration (P<0.0001). The expression of iNOS and IL-6 mRNA and protein were down-regulated by hemin (P<0.001). Hemin is effective in inducing HO-1 and in reducing the ocular inflammation induced by LPS probably by down-regulating NO and pro-inflammatory cytokine expression.     

Inhibitory effects of pyrrolidine dithiocarbamate on endotoxin-induced uveitis in Lewis rats

PURPOSE: To determine the effect of pyrrolidine dithiocarbamate (PDTC), an antioxidant nuclear factor (NF)-kappaB inhibitor, on the ocular inflammation induced by lipopolysaccharide (LPS). METHODS: Endotoxin-induced uveitis (EIU) was produced by a footpad injection of 200 microg LPS in male Lewis rats. PDTC (200 mg/kg) was injected intraperitoneally 30 minutes before the LPS administration. The number of infiltrating cells and protein concentration in the aqueous humor (AqH) was determined from the AqH collected at 24 hours. Immunohistochemical staining with a monoclonal antibody against activated NF-kappaB was performed to evaluate the effect of PDTC on NF-kappaB activation. Interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA expression in the iris-ciliary body (ICB) was determined by RNase protection assay (RPA). The levels of these cytokines and nitric oxide (NO) production were also determined. RESULTS: The number of cells in the AqH was 1100 +/- 254 cells/microL in rats injected with LPS and 90 +/- 43 cells/microL in rats pretreated with PDTC (P < 0.001). The concentration of proteins was significantly lower in the AqH of rats pretreated with PDTC than in those without PDTC. The number of activated NF-kappaB-positive cells in the ICB was reduced by the PDTC treatment. The ICB at 6 hours after LPS injection exhibited increased expression of IL-1beta, IL-6, and TNF-alpha mRNAs, which was decreased after PDTC pretreatment. PDTC also significantly diminished the levels of these cytokines and nitrite-nitrate in the AqH. CONCLUSIONS: These results suggest that PDTC reduces ocular inflammation in eyes with EIU by downregulating proinflammatory cytokine expression and by inhibiting the NF-kappaB-dependent signaling pathway.     

IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis

PURPOSE: To determine the immunosuppressive status of aqueous humor (AqH) from mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the relevant cytokines responsible for immunomodulatory activity within EIU AqH. METHODS: Bacterial lipopolysaccharide (LPS) was injected into hind footpads of C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was evaluated for content of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma and capacity to suppress anti-CD3-driven T-cell proliferation. Cytokine mRNA expression in iris-ciliary body (I/CB) was analyzed by RNase protection assays. RESULTS: During 6 to 24 hours after LPS injection, total TGF-beta levels in AqH increased even though the fluid lost its capacity to suppress T-cell activation. At this time, AqH contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its capacity to suppress T-cell activation, which correlated with high levels of TGF-beta. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of normal mice prevented antigen-specific anterior chamber-associated immune deviation (ACAID). CONCLUSIONS: LPS-induced intraocular inflammation is associated with local production of IL-6, which robs AqH of its immunosuppressive activity, perhaps by antagonizing TGF-beta. The fact that IL-6 antagonized ACAID induction in normal eyes suggests that strategies to suppress the intraocular synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.     

TLR4-MyD88在大鼠急性前葡萄膜炎虹膜中的表达

目的观察内毒素诱导的大鼠急性前葡萄膜炎（EIU）虹膜组织内Toll样受体4（TLR4）、髓样分化因子88（MyD88）及核因子-κBp65（NF-κB p65）的表达。方法Wistar大鼠50只,随机分为5组,0、12、24、48、72h,每组10只。0h组为正常对照组,其余4组均足垫部注射霍乱弧菌内毒素脂多糖（LPS）200μg,建立EIU动物模型,每隔2h用裂隙灯观察大鼠眼前节炎症反应。通过铺片免疫组织化学染色,检测虹膜睫状体组织内TLR4、MyD88和NF—κB p65的表达,并对虹膜内TLR4^＋和MyD88^＋及NF—κB p65^＋细胞进行计数。结果注射后24～48h大鼠眼前段的炎症反应达到高峰,72h炎症反应逐渐缓解。组织病理学检查表明,虹膜睫状体组织的炎性细胞浸润在24～48h达到高峰,与临床反应结果相符。TLR4在模型鼠虹膜睫状体炎复合体中表达的免疫组织化学检测结果表明,0h组虹膜铺片内无阳性细胞,12h后可见细胞形态大多为类圆形的阳性细胞,48h达高峰,72h阳性细胞数开始减少,各组阳性细胞数总体差异有统计学意义（F=46．79,P〈0．05）。MyD88和NF—κB p65的表达与TLR4的改变趋势相一致（F=54．37,P〈0．05;F=85．32,P〈0．05）。结论内毒素诱导的EIU虹膜内,TLR4及其下游信号传导分子的表达量发生改变,提示TLR4-MyD88依赖传导途径可能参与了EIU的发病.     

Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats

PURPOSE: Lutein deposits in the macula and lens of human eyes with high concentration and is well known as an eye-protective nutrient for its beneficial effects on eye disease such as age-related macular degeneration and cataract. The purpose of the present study was to investigate the effects of lutein on endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in male Lewis rats by subcutaneous injection of 200 microg lipopolysaccharide. Lutein or dexamethasone was administered intravenously at 30 minutes before, at the same time as, and at 30 minutes after LPS treatment. The aqueous humor was collected at 24 hours after LPS injection, the number of infiltrating cells, the protein concentration, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, prostaglandin (PG)-E2, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-2 in the aqueous humor were determined. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappaB was performed to evaluate the effect of lutein on NF-kappaB activation in the iris-ciliary body (ICB) of rats. A mouse macrophage cell line (RAW264.7 cells) was stimulated with LPS in the presence or absence of lutein. Expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and degradation of inhibitor kappaB (IkappaB) were analyzed by Western blot analysis. RESULTS: Lutein suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg lutein was as strong as that of 1 mg/kg dexamethasone. Treatment with lutein reduced the concentrations of NO, TNF-alpha, IL-6, PGE2, MCP-1, and MIP-2 in aqueous humor. Lutein also suppressed the activation of NF-kappaB in the ICB as well as iNOS and COX-2 expression and IkappaB degradation in RAW cells. CONCLUSIONS: These findings indicate that lutein has anti-inflammatory effects on EIU by inhibiting the NF-kappaB dependent signaling pathway and the subsequent production of proinflammatory mediators.     

Inhibitory effects of antithrombin III against leukocyte rolling and infiltration during endotoxin-induced uveitis in rats

PURPOSE: This study was designed to investigate the suppressive effects of antithrombin (AT)III on inflammatory reactions during endotoxin-induced uveitis (EIU) in rats by studying leukocyte-endothelium interactions. METHODS: EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). ATIII was administered immediately after or at 6 hours after LPS injection. Its suppressive effects on inflammatory leukocyte behavior were evaluated in vivo with acridine orange digital fluorography. Clinical signs of inflammation were also examined, and aqueous humor (AH) was collected to evaluate leukocyte infiltration and protein leakage. In a separate experiment, P-selectin mRNA expression was studied in the iris-ciliary body (ICB) and the retina. RESULTS: After treatment with ATIII, leukocyte rolling was substantially inhibited along the retinal veins, suppressing subsequent leukocyte infiltration into the vitreous cavity. Similarly, leukocyte infiltration and protein leakage into the AH were significantly reduced with ATIII treatment. The clinical grade of EIU was substantially lower in ATIII-treated rats. In addition, delayed administration of ATIII after EIU induction significantly attenuated these inflammatory reactions. The levels of P-selectin mRNA expression in both ICB and retina, which were upregulated after LPS injection, were substantially lower in the ATIII-treated rats. CONCLUSIONS: ATIII treatment significantly inhibited inflammatory reactions induced with LPS. Its suppressive effects on P-selectin expression could contribute to the attenuation of leukocyte infiltration, possibly by inhibiting leukocyte rolling. The current findings suggest that ATIII may have a role in the management of patients with uveitis.     

Contribution of TNF-alpha to leukocyte adhesion,vascular leakage,and apoptotic cell death in endotoxin-induced uveitis in vivo

PURPOSE: To investigate the effect of TNF-alpha on leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis (EIU) in the rat. METHODS: EIU was induced in Long-Evans rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. A single injection of recombinant TNF receptor P75 (etanercept) was given subcutaneously 24 hours before the administration of LPS. Twenty-four hours after administration of LPS, leukocyte adhesion was evaluated in vivo with SLO-acridine orange angiography and ex vivo with concanavalin A lectin staining of retinal flatmounts. Neutrophil activation was quantified by a myeloperoxidase activity assay. Vascular leakage was assessed by Evans blue extravasation. Retinal cell death was assessed with TUNEL staining and quantified with a modified ELISA protocol. Involvement of caspase-3 and -8 was determined by M30 antibody staining, Western blot analysis, and a test for enzymatic activity. RESULTS: Twenty-four hours after the LPS injection, significant increases in leukocyte rolling, adhesion, and activation were observed. In addition, increased levels of apoptosis in the vascular endothelium and the ganglion cell and inner nuclear layers and activation of caspase-8 and -3 were observed. After administration of the TNF-alpha inhibitor, significant reduction in the leukocyte rolling, adhesion, activation, and apoptosis in all the affected layers was observed. The quantitative analysis of vascular leakage revealed a significant decrease after treatment with etanercept. Retinal cell death quantification showed a significant decrease after treatment with the TNF-alpha inhibitor. CONCLUSIONS: Anti-TNF-alpha treatment reduces the LPS-induced increases in leukocyte rolling, adhesion, and vascular leakage in this rat model of inflammatory uveitis. These results suggest the involvement of TNF-alpha in inflammatory uveitis and its potential use as a therapeutic agent in the reduction of ocular inflammation.     

A cholinergic agonist attenuates endotoxin-induced uveitis in rats

PURPOSE: Investigation of physiological anti-inflammatory mechanisms can contribute to the treatment of inflammatory disorders. The purpose of the present study was to investigate the effect of nicotine, a selective cholinergic agonist, on endotoxin-induced uveitis (EIU) in rats and the underlying molecular mechanism. METHODS: Lipopolysaccharide (LPS; endotoxin) and nicotine were injected intraperitoneally. Clinical scores were evaluated by slit lamp. Intracameral protein content and the number of cells were determined. Immunohistochemical reactivity of alpha7 nicotine acetylcholine receptor (alpha7nAChR) was examined in the iris and ciliary body (ICB). mRNA and protein levels of cytokines and chemokines were measured by real-time PCR and enzyme-linked immunosorbent assay. RESULTS: After LPS injection, clinical scores, as well as protein content and number of cells in the aqueous humor increased during 18 to 36 hours. Nicotine inhibited the endotoxin-induced elevation of these levels. mRNA and protein of alpha7nAChR expression levels were significantly increased by LPS and/or nicotine injection. Nicotine showed no effects on endotoxin-induced elevation of mRNA levels in ICB. However, nicotine decreased the endotoxin-induced elevation of interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC)-1, and monocyte chemotactic protein (MCP)-1, but did not affect IL-10 in the serum and aqueous humor. CONCLUSIONS: Nicotine attenuated endotoxin-induced uveitis through directly decreasing the levels of multiple cytokines and chemokines in the aqueous humor, but did not affect the mRNA levels of these factors. The findings suggest that the nicotinic anti-inflammatory pathway may be involved in the pathogenesis of EIU.     

The effect of infliximab, cyclosporine A and recombinant IL-10 on vitreous cytokine levels in experimental autoimmune uveitis

BACKGROUND: To identify the effect of infliximab, cyclosporine A and recombinant IL-10 in experimental autoimmune uveitis. MATERIALS AND METHODS: Sixty male rats were assigned to five groups of 12 each. All the groups (except the control group) were administered 30 microg retinal-S antigen intraperitoneally. On the 14th day, after confirmation of uveitis with histopathological study, daily cyclosporine A injection was given in cyclosporine A treatment group and physiological serum in the uveitis-induced placebo treatment and control groups. In the infliximab treatment group, infliximab was administered on the 14th, 15th, 17th, 19th and 21st days. In the recombinant IL-10 treatment group, three doses of recombinant IL-10 were given four hours and a half hours before and eight hours after retinal-S antigen administration. On the 21st day of the study, all rats were sacrificed and vitreous cytokine levels (IL-1, IL-6, IL-8 and TNF-alpha) were studied with ELISA. RESULTS: In the treatment groups, cytokine levels (IL-1, IL-6 and TNF-alpha) were significantly lower than the uveitis-induced placebo treatment group. Compared with the control group, there was no significant difference with respect to TNF-alpha and IL-8 in the infliximab treatment group; IL-8 in the cyclosporine A treatment group; IL-6 and IL-8 in the recombinant IL-10 treatment group. The drugs used did not significantly differ in respect to their effects on vitreous IL-6, IL-8 and TNF-alpha levels. CONCLUSION: Cyclosporine A, infliximab and recombinant IL-10 reduce the vitreous cytokines levels. Among these drugs, recombinant IL-10, which is still in its experimental phase, might be considered as a new therapeutic agent.     

Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo

The aim of the present study was to investigate the effects of blue honeysuckle extract (BHE), which contains high level of phenolic compounds, on endotoxin-induced uveitis (EIU). Male Lewis rats were randomly divided into 5 groups with 14 rats in each (eight rats for collection of aqueous humor, six rats for histologic examination). EIU was induced by a footpad injection of lipopolysaccharide (LPS). 1, 10, or 100 mg of BHE was injected intravenously immediately after LPS injection. The aqueous humor was collected at 24 h after LPS injection, the number of infiltrating cells, protein concentration, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and prostaglandin (PG)-E2 levels in the aqueous humor were determined. Some eyes were enucleated for histologic examination and immunohistochemical analysis. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappaB was performed to evaluate the effect of BHE on NF-kappaB activation. To further clarify the anti-inflammatory effect, RAW264.7 cells (a mouse macrophage cell line) were stimulated with LPS in the presence or absence of BHE and its major phenolics, cyanidin 3-glucoside (C3G), cyanidin 3-rutinoside (C3R), chlorogenic acid (CA). Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by Western blot method. BHE treatment significantly reduced the inflammatory cell infiltration, the protein concentration, the levels of NO, TNF-alpha and PGE2 in the aqueous humor and improved histologic status of the ocular tissue. The number of activated NF-kappaB-positive cells was lower in the iris-ciliary body treated with BHE at 3 h after LPS injection. BHE significantly suppressed the production of NO, PGE2 and TNF-alpha in the culture medium as well as the expression of iNOS and COX-2 by LPS-stimulated RAW264.7 cells in a dose-dependent fashion. C3G, C3R and CA showed no or weak inhibitory effects on the level of inflammatory mediators and the expression of iNOS and COX-2. These results suggest that BHE attenuates the degree of inflammation in eyes with EIU by inhibiting the NF-kappaB dependent signaling pathway and the subsequent production of proinflammatory mediators.     

Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo

The aim of the present study was to investigate the efficacy of fucoxanthin on endotoxin-induced uveitis (EIU) in rats. The effects of fucoxanthin on endotoxin-induced leucocyte and protein infiltration, nitric oxide (NO), prostaglandin (PG)-E2 and tumour necrosis factor (TNF)-alpha concentrations in rat aqueous humour, as well as on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in a mouse macrophage cell line (RAW 264.7 cells) were studied. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS injection, either 0.1, 1 or 10mgkg(-1) of fucoxanthin was injected intravenously. The aqueous humour was collected 24hr later from both eyes, and both the number of cells infiltrating into the aqueous humour and the aqueous humour protein concentration were measured. The levels of PGE2, NO and TNF-alpha were determined by enzyme-linked immunosorbent assay. The RAW 264.7 cells were pretreated with various concentrations of fucoxanthin for 24hr and subsequently incubated with LPS for 24hr. COX-2 and iNOS protein expression was analysed by the Western blotting method. Levels of PGE2, NO and TNF-alpha production were determined. Fucoxanthin suppressed the development of EIU in a dose-dependent fashion. Treatment with fucoxanthin resulted in a reduction in PGE2, NO and TNF-alpha concentrations in the aqueous humour. The expression of COX and iNOS protein in the fucoxanthin treated RAW264.7 cells decreased significantly compared to that the LPS group. It also significantly reduced the concentration of PGE2, NO and TNF-alpha production in the medium of cells. The present result indicate fucoxanthin suppresses the inflammation of EIU by blocking the iNOS and COX-2 protein expression and its anti-inflammatory effect on eye is comparable with the effect of predinisolone used in similar doses.     

Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6.

The potential role of interleukin-6 (IL-6) was studied as an inflammatory mediator of endotoxin (or lipopolysaccharide [LPS])-induced uveitis (EIU) in the rat. In young Lewis rats, levels of intraocular IL-6, but not serum IL-6, correlated with the severity of uveitis and with aqueous humor protein levels in response to foot pad injections of LPS (P less than 0.001). Adult Lewis rats did not develop uveitis and had no intraocular IL-6, although IL-6 was released systemically. Resistance to EIU and absence of IL-6 levels in the aqueous humor, despite the ability to release serum IL-6, also were observed in brown Norway rats, irrespective of age and weight. Intravitreal injection of as little as 1 ng of human recombinant IL-6 induced uveitis in young Lewis rats. In adult Lewis rats, and in young animals made tolerant to LPS, intravitreal IL-6 still caused substantial leakage of plasma proteins into the anterior chamber but no influx of inflammatory cells. As early as 2 hr after intravitreal injection of IL-6, immunohistochemical analysis showed invasion of the iris, corneal stroma, and anterior chamber by polymorphonuclear leukocytes (PMN) and expression of major histocompatibility complex (MHC) class II antigen in the retina by large cells that were macrophage-marker ED2 negative. This was followed by massive PMN infiltration of the retinal layers and vitreous. The MHC class II antigen expression of ciliary and iris epithelium occurred at a later stage (greater than 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)     

红芪多糖干预内毒素诱导的葡萄膜炎模型中糖原合成酶3-β的表达及其作用机制

目的　通过观察红芪多糖（radix hedysari polysaccharide，HPS）和氯化锂（LiCl）对霍乱弧菌内毒素（lipopolysaccharide,LPS）诱导的葡萄膜炎的抗炎作用，探讨糖原合成酶3-β（glycogen synthase kinase 3-β，GSK3-β）在葡萄膜炎中的作用机制。方法　200只Wistar大鼠随机分为4组(n=50):空白对照组（negative control，NC）组、LPS诱导的葡萄膜炎组（LPS组）、HPS治疗组（LPS+HPS组）和LiCl治疗组（LPS+LiCl组）。LPS+HPS组腹腔注射400 mg·kg^-1 HPS，LPS+LiCl组腹腔注射0.5 mol·L^-1的LiCl 100 μL，对照组和LPS组注射等量PBS。2 h后，LPS组、LPS+HPS组和LPS+LiCl组每只大鼠足底注射0.1 mL LPS注射液，NC组注射等体积的PBS。应用临床评分、裂隙灯照相、HE染色等检查评价炎性反应程度；Western blot和RT-PCR检测虹膜睫状体GSK3-β和核因子-κB（neuclear factor-κB，NF-κB） p65表达水平；酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测大鼠前房房水中肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素6（interleukin-6，IL-6）、白细胞介素10（interleukin-10，IL-10）、白细胞介素1β（interleukin-1β，IL-1β）等细胞因子的水平。结果　LPS注射后6 h、12 h、24 h、48 h LPS组的炎症评分分别为（2.3±0.2）分、（3.6±0.7）分、（3.9±0.3）分、（3.2±0.4）分，显著高于其他三组（均为P<0.05），而LPS+HPS组、HPS+LiCl组和NC组之间差异均无统计学意义（均为P>0.05），HPS或LiCl预处理对LPS诱导的大鼠葡萄膜炎产生了抗炎效果。经过HPS或LiCl处理，LPS诱导的葡萄膜炎大鼠虹膜睫状体磷酸化GSK3-β水平上调，NF-κB p65表达明显被抑制，前房房水中抗炎因子IL-10水平上调，而TNF-α、IL-6、IL-1β等炎症细胞因子受到抑制。结论　HPS或LiCl预处理可以抑制LPS诱导的大鼠葡萄膜炎炎性反应，这一抗炎作用与GSK3-β的抑制性磷酸化密切相关。