白三烯类化合物(Leukotrienes)对小鼠腹腔巨噬细胞生成白细胞介素6的影响

探讨了白三烯Ｂ４（ＬＴＢ４）、白三烯Ｃ４（ＬＴＣ４）及白三烯Ｄ４（ＬＴＤ４）对小鼠腹腔巨噬细胞分泌白细胞介素６（ｉｎｔｅｒｌｅｕｋｉｎ６，ＩＬ６）的影响。用ＩＬ６依赖细胞株Ｂ９的ＭＴＴ方法测定样品中ＩＬ６的含量。结果显示，ＬＴＢ４能剂量依赖性地增加巨噬细胞培养上清液中ＩＬ６的含量。ＬＴＣ４及ＬＴＤ４促进巨噬细胞培养上清液中ＩＬ６含量的最适浓度分别为：６９×１０－８和８０５×１０－８ｍｏｌ·Ｌ－１。结果提示：ＬＴＢ４与ＬＴＣ４及ＬＴＤ４在某些生物学功能方面有一致性。与ＬＴＣ４及ＬＴＤ４相比，ＬＴＢ４促进巨噬细胞培养上清液中ＩＬ６的含量的最适浓度则要大１～２个数量级，提示在炎症反应中，肽白三烯与ＩＬ６的相关性较强。

Cysteinyl leukotrienes and their receptors: Bridging inflammation and colorectal cancer

Long-standing inflammation has emerged as a hallmark of neoplastic transformation of epithelial cells and may be a limiting factor of successful conventional tumor therapies.A complex milieu composed of distinct stromal and immune cells,soluble factors and inflammatory mediators plays a crucial role in supporting and promoting various types of cancers.An augmented inflammatory response can predispose a patient to colorectal cancer(CRC).Common risk factors associated with CRC development include diet and lifestyle,altered intestinal microbiota and commensals,and chronic inflammatory bowel diseases.Cysteinyl leukotrienes are potent inflammatory metabolites synthesized from arachidonic acid and have a broad range of functions involved in the etiology of various pathologies.This review discusses the important role of cysteinyl leukotriene signaling in linking inflammation and CRC.

Effects of Prostaglandins and Leukotrienes on Hypoxic Pulmonary Vasoconstriction in Rats

To investigate the effects of prostaglandins (PGs) and leukotrienes (LTs) on hypoxic pulmonary vasoconstriction (HPV), in vivo rats experiment and in vitro perfused lung experiment were conducted. The effect of hypoxia on hemodynamics, concentrations of TXB 2 and 6 keto PGF 1α in serum and lung tissue during hypoxia and effects of PGs and LTs on HPV were observed. The results showed that pulmonary arterial pressure (P pa ) and pulmonary vascular resistance were increased during hypoxia, but cardiac output and systemic arterial pressure were decreased. There were increases of the concentrations of TXB 2 and 6 keto PGF 1α and their ratio in serum and lung tissue during hypoxia. After use of cyclooxygenase inhibitor (indomethacin) in vivo and in vitro , HPV was augmented respectively, but after use of lipoxygenase inhibitor (diethylcorbamazine) or leukotriene receptor blocker (LY 171883), HPV was attenuated. It was suggested that LTs mediated pulmonary vasoconstriction, PGs inhibited pulmonary vasoconstriction and they played a modulating role during hypoxia.

Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis

Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Enhanced expressions and activations of leukotriene C4synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model

AIM： To investigate the expression and activity of leukotriene C4 （LTC4） synthesis enzymes and their underlying relationship with cysteinyl leukotriene （cys-LT） generation in a rat fulminant hepatic failure （FHF） model induced by D-galactosamine/lipopolysaccharide （D-GaIN/ LPS）. METHODS： Rats were treated with D-GaIN （300 mg/kg） plus LPS （0.1 mg/kg） for 1, 3, 6, and 12 h. Enzyme immunoassay was used to determine the hepatic cys-LT content. Reverse transcription-polymerase chain reaction （RT-PCR）, Western blot or immunohistochemical assay were employed to assess the expression or location of LTC4 synthesis enzymes, which belong to membrane associated proteins in eicosanoid and glutathione （MAPEG） metabolism superfamily. Activity of LTC4 synthesis enzymes was evaluated by determination of the products of LTA4 after incubation with liver microsomes using high performance liquid chromatography （HPLC）. RESULTS： Livers were injured after treatment with D-GaIN/LPS, accompanied by cys-LT accumulation at the prophase of liver injury. Both LTC4 synthase （LTC4S） and microsomal glutathione-S-transferase （mGST） 2 were expressed in the rat liver, while the latter was specifically located in hepatocytes. Their mRNA and protein expressions were up-regulated at an earlier phase after treatment with D-GaIN/LPS. Meantime, a higher activity of LTC4 synthesis enzymes was detected, although theactivity of LTC4S played the main role in this case. CONCLUSION： The expression and activity of both LTC4S and mGST2 are up regulated in a rat FHF model, which are, at least, partly responsible for cys-LT hepatic accumulation.

A New Therapy for Human Endometriosis: The Therapeutic Value of Leukotriene Receptor Antagonist for Endometriosis

Some drugs that regulate estrogen are currently used as therapy for endometriosis. However, these medical treatments have significant side effects and patients who hope to become pregnant cannot overcome infertility. To compare morphological alterations and clinical symptoms, revised American Fertility Society (r-AFS) scores were compared between patients with and without leukotriene receptor antagonist (LTR-A) treatment. LTR-A-treated cases showed significantly decreased r-AFS score. Furthermore, a significant correlation was seen between r-AFS score and LTR-A treatment period. In treated cases, clinical symptoms decreased and some patients achieved pregnancy. Morphologically, lesions in LTR-A-treated cases showed apoptotic fibroblasts and degeneration of collagen fibers. Our findings revealed that LTR-As had significant therapeutic value for the treatment of human endometriosis. Anti-LT therapy appears efficacious not only in the treatment of clinical symptoms and lesions, but also in improving fertility.

Inhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene release

Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FcεRI, on LAD2 cells. The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treatment of allergic disease.

Kinetics of Serum and Local Leukotriene B₄Response in Experimental Intravaginal Trichomoniasis by <i>T. vaginalis</i>Isolates from Symptomatic and Asymptomatic Women

Trichomoniasis is most common sexually transmitted disease caused by T. vaginalis. The clinical manifestation varies from severe manifestation to asymptomatic condition. However, the exact virulence markers led to varied symptomatology was not well clarified. The role of leukotriene B4 (LTB4) in the pathogenesis of many parasitic diseases has been reported. The present study reports the leukotriene B4 levels on different days post infection (3rd, 7th, 14th, 21st and 28th d.p.i.) in serum and vaginal washes (VWs) and vaginal tissues of mice infected intravaginally with T. vaginalis isolates from 10 symptomatic and 10 asymptomatic women. A significant increase in LTB4 was observed on the 3rd to 28th d.p.i. in serum and VWs of mice infected with T. vaginalis isolates from asymptomatic as compared to symptomatic women. The present study also reports the histopathological changes of the posterior vaginal fornix’s and upper portion of the vagina of mice infected intravaginally with T. vaginalis isolates from 10 symptomatic and 10 asymptomatic women. The results show that there are no significant differences between symptomatic and asymptomatic isolates regarding histopathological changes.

Involvement of cysteinyl leukotriene signaling in microglial morphological changes and CASP1 expression in vitro

OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.

The effects of 5-lipoxygenase inhibitor and cysteinyl leukotriene receptor 1 antagonist on 1-methyl-4-phenylpyridine-induced neurotoxicity

OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.

Modified reversed-phase high performance liquid chromatography for the determination of leukotriene B_4 and 5-hydroxyeicosatetraenoic acid in peripheral neutrophils of rabbits

Modification was made on the reversed-phase high performance liquid chromatography(RP-HPLC)with Yue et al's method as a base.The modified RP-HPLC was used to detect leukotriene B_4(LTB_4)and 5-hydroxyeicosatetraenoic acid(5-HETE).It was found that the modified method has the merits of simpler procedures,shorter testing time and more satisfactory efficacy.

Mast Cell Infiltration and Leukotriene Receptor Expression in Various Tumors: Possible Clinical Application of Common Pathological Findings Concerned with Tumor Development

Since the mechanisms of the developmental processes of tumors remain unclear, early detection and early treatment of the tumors is necessary to save patients with malignant tumors. Therapies currently available to patients are surgery, chemotherapy, and radiotherapy. However, there are many patients who cannot be saved by such therapies. In this study, we found the common features of various tumor tissues, and we demonstrated the effect of therapeutics that target them by using experimental rats with spontaneous tumors. 26 kinds of human tumors (epithelial or mesenchymal origin, and malignant or benign) and Sprague-Dawley rats with spontaneous mammary gland tumors were examined by light and electron microscope. To detect of mast cells and leukotriene receptor, toluidine blue stain and immunohistochemical stain were performed. The rats were orally administered one of leukotriene receptor antagonists. We found that the presence of numerous mast cells and expression of leukotriene receptors in various tumor (human tumors and rat spontaneous tumors). And the therapeutic effects, which suppressed not only tumor progress but also angiogenesis and nerve formation, for rat tumors by administration of leukotriene receptor antagonist could obtain. Our data suggest the possibility that allergic reactions, in which leukotriene and leukotriene receptors in particular appear to play an important role, are involved in the development and progression of tumors and that it may be possible to control tumor progression by regulating such reactions. Our results might be useful for clinical applications of oncotherapy.

The effect of Shufengzhitong decoction combined with four cervical needles on cervical spondylotic radiculopathy and leukotriene and inflammatory factors

Objective:To investigate the effect of shufengzhitong decoction combined with four cervical needles on cervical spondylotic radiculopathy(CSR)and leukotriene and inflammatory factors.Methods:110 patients with CSR were randomly divided into two groups,with 55 in each group.There was no significant difference in baseline data between the two groups(P>0.05).The control group were treated with Shufeng Zhitong decoction orally,and the treatment group were treated with four neck acupuncture on the basis of the control group.Neck pain scale score(NPQ),Cervical spondylosis clinical evaluation scale score(CASCS)Cervical range of motion score(CROM),Emg surface signal and serum Levels of leukotriene B4(LTB4),leukotrieneC4(LTC4),leukotrieneD4(LTD4),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,IL-8 and IL-18 were compared before and after treatment.The clinical effect of the two groups was compared.Results:NPQ of the treatment group was lower than that of the control groupafter treatment(P<0.01),the scores of CASCS and CROM were higher than those of the control group(P<0.01),the median frequency of surface EMG signal of biceps brachii and superior trapezius muscle were higher than those of the control group(P<0.01),the levels of serum LTB4,LTC4,LTD4,IL-1β,TNF-α,IL-6,IL-8 and IL-18 were lower than those of the control group(P<0.01),the clinical effect was better than that of the control group(P<0.05),and the differences were statistically significant.Conclusion:Shufengzhitong decoction combined with cervical four acupuncture can effectively alleviate the symptoms of cervical spondylosis,regulate the myoelectric signal of muscle surface,reduce the content of leukotriene in serum,reduce the expression of inflammatory factors,and it has a significant effect on the treatment of CSR.

Efficacy and anti-inflammatory analysis of glucocorticoid,antihistamine and leukotriene receptor antagonist in the treatment of allergic rhinitis

BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.

5-Lipoxygenase and cysteinyl leukotriene receptors in neuroinflammation and neuronal injury

Brian ischemic injury and central neurodegenerative diseases as leading contributors to disability and death have become a majorclinical and public health concern worldwide.Neuroinflammation plays a pivotal role in the pathological progression of cerebral ischemia and neurodegenerative diseases including Parkinson disease(PD).Therefore,it is important to find effective therapeutic targets to attenuate inflammation and delay the progression of brain injury.Cysteinyl leukotrienes(CysLTs) are potent inflammatory mediators synthesized from arachidonic acid by 5-lipoxygenase(5-LOX) in the central nervous system.Two distinct G-protein-coupled receptors,CysLT1 R and CysLT2 R,mediate most of the known CysLTs biological responses.Accumulating evidence has demonstrated that postischemic inflammation and neuronal loss are mediated by 5-LOX and CysLTRs fol owing focal cerebral ischemia.We recently reported that the expression of 5-LOX,CysLT1R and inflammatory vascular cell adhesion molecule-1(VCAM-1) was upregulated in the hippocampus of rats with transient global cerebral ischemia,which was closely associated with delayed neuronal death in the hippocampal CA1 area.5-LOX inhibitor zileuton,CysLT1R antagonist ONO-1078 and montelukast dose-dependently reduced hippocampal CA1 neuronal death and inhibited the increased expression of 5-LOX and VCAM-1.In vitro ischemia-like injury in 5-LOXtransfected PC12 cells,oxygen-glucose deprivation(OGD) induced cell death mediated by5-LOX via ROS/P38 MAPK pathway.The nonselective 5-LOX inhibitor caffeic acid inhibited OGDstimulated activation of 5-LOX and ROS/P38 MAPK signaling and improved neuronal survival.In PD model,high concentrations of rotenone caused directly PC12 neurotoxicity,which was modulated by 5-LOX and abolished by suppression of 5-LOX.It is well known that microglia is major modulators of inflammatory response after brain injury.Overactivated microglia and production of proinflammatory cytokine IL-1β,IL-6 and TNF-α contribute to the neuroinflammation and brain injury.5-LOX,CysLT1R and CysLT2R are involved in microglial activation and resultant neurotoxic responses.It has been found that low concentrations of rotenone can activate 5-LOX and CysLT1R on microglial cells to enhance microglial inflammation and microglia-dependent neuronal death in vitro.5-LOX inhibitor zileuton and CysLT1R antagonist montelukast protected neurons from microglia-dependent rotenone neurotoxicity.Furthermore,lipopolysaccharide(LPS)induced microglial activation and microglial neurotoxicity mediated by CysLT2R in vitro.Both pharmacological blockade(CysLT2R antagonist HAMI3379) and RNA interference(specific short hairpin RNA) of CysLT2 R significantly attenuated LPS-triggered microglial inflammation and subsequent neuronal death.Collectively,the present results indicate the role of 5-LOX and CysLTRs in neuroinflammation and brain injury.Modulation of 5-LOX and CysLTRs may be potential therapeutic approaches for inflammation-related brain disorders such as cerebral ischemia and PD.However,further research is needed to clarify the mechanisms underlying the regulation of neuinflammatory processes by 5-LOX and CysLTRs.

Effects of selenium and vitamin E deficiencies on level of leukotriene C_4

ＥｆｆｅｃｔｓｏｆｓｅｌｅｎｉｕｍａｎｄｖｉｔａｍｉｎＥｄｅｆｉｃｉｅｎｃｉｅｓｏｎｌｅｖｅｌｏｆｌｅｕｋｏｔｒｉｅｎｅＣ_４ＬｉｕＷｅｉ－Ｍｉｎ（刘为民）；ＹｕｅＬｉ－Ｊｉｅ（岳丽杰）；ＬｉＧｕａｎｚ－Ｓｈｅｎｇ（李广生）ａｎｄＺｈａｎｇＸｉｕ－Ｙ?..

Relationship of cyclic stretching of human patellar tendon fibroblasts with abnormal increase of prostaglandins E2 and leukotriene B4

To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.

醋炙柴胡对抑郁症小鼠治疗的增效减毒作用研究

目的探讨醋炙柴胡对抑郁症小鼠治疗的增效减毒作用。方法70只雄性C57小鼠随机分为对照组、模型组、帕罗西汀组(10 mg/kg)、生柴胡低剂量组(1.5 g/kg)、生柴胡高剂量组(12 g/kg)、醋炙柴胡低剂量组(1.5 g/kg)、醋炙柴胡高剂量组(12 g/kg),每组10只。除对照组外,其他组小鼠均采用慢性不可预知温和应激法构建抑郁模型,再相应给药处理15 d,对照组、模型组以等体积生理盐水替代。通过糖水消耗实验、旷场实验及强迫游泳实验评价小鼠抑郁样行为,检测各组小鼠肝功能,HE染色观察肝组织病理变化,酶联免疫吸附试验检测肝组织中脂质过氧化物含量。结果与对照组比较,模型组糖水偏好率、进入旷场中心区域时间降低,游泳不动时间延长,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆汁酸(TBA)及肝组织丙二醛、4-羟壬烯醛和白三烯B4含量升高(P<0.05)。与模型组比较,生柴胡低剂量组、醋炙柴胡低和高剂量组、帕罗西汀组糖水偏好率升高,生柴胡低和高剂量组、醋炙柴胡低和高剂量组、帕罗西汀组进入旷场中心区域时间延长,游泳不动时间缩短,ALT、AST、TBA、4-羟壬烯醛和白三烯B4明显降低,醋炙柴胡低和高剂量组、帕罗西汀组丙二醛降低(P<0.05),以醋炙柴胡低剂量组效果最佳。生、醋炙柴胡组肝组织病理变化改善。结论醋炙柴胡对抑郁症小鼠的增效减毒作用优于生柴胡。

血清sFlt-1、LTB4对颅内动脉瘤介入栓塞术后脑血管痉挛的预测价值

目的 探讨颅内动脉瘤患者血清可溶性血管生长因子受体(sFlt-1)、白三烯B4(LTB4)对介入栓塞术后脑血管痉挛(CVS)的预测价值。方法 选取2019年1月至2023年9月本院收治的98例颅内动脉瘤患者为观察组,依据术后3~5 d内是否发生CVS分为CVS组(32例)和无CVS组(66例);选取102例同期本院健康体检者作为对照组。采用酶联免疫吸附法检测血清sFlt-1、LTB4水平。采用Logistic回归分析颅内动脉瘤介入栓塞术后CVS的影响因素。采用受试者工作特征(ROC)曲线分析血清sFlt-1、LTB4水平对颅内动脉瘤介入栓塞术后CVS的预测价值。结果 观察组患者血清sFlt-1、LTB4水平均高于对照组,差异有统计学意义(P<0.05)。CVS组患者血清sFlt-1、LTB4水平及术后血压波动范围≥30 mmHg、Hunt-Hess分级Ⅲ级比例均高于无CVS组,差异有统计学意义(P<0.05)。sFlt-1(OR:2.985;95%CI:1.684~5.291)、LTB4(OR:2.868;95%CI:1.581~5.204)是颅内动脉瘤介入栓塞术后CVS的独立危险因素(P<0.05)。sFlt-1、LTB4单独及联合预测颅内动脉瘤介入栓塞术后CVS的曲线下面积(AUC)分别为0.839、0.825、0.915,敏感度分别为84.44%、87.59%、81.36%,特异度分别为74.26%、75.87%、90.98%,两者联合的AUC高于sFlt-1、LTB4单独的AUC,差异均有统计学意义(Z=2.150、2.546,P<0.05)。结论 颅内动脉瘤介入栓塞术后CVS患者血清sFlt-1、LTB4水平升高,二者联合检测可作为预测CVS的重要指标。