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.

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.

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.

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.

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.

Aggravated inflammation and increased expression of cysteinyl leuko-triene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.

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.

Effects of leukotriene receptor antagonist on chronic obstractive pulmonary disease induced pulmonary hypertension

Objectives To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.Methods Eleven cases of chronic cor pulmonale at acute exacerbation were examinted using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E4 (LTE4) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Artarial and mixed venous blood gas analyses were done correspondingly.Results The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE4 and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP. Conclusions Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.

白三烯受体拮抗剂在儿童变应性鼻炎中的临床应用专家共识(2023,广州)

半胱氨酸白三烯(CysLT)是免疫细胞合成和分泌的炎性介质,与细胞膜上的受体结合发挥生物学效应,参与多种过敏性疾病的发病。抗白三烯药物有两类:CysLT1受体拮抗剂(LTRA)和白三烯合成抑制剂,前者与CysLT1受体结合,从而干扰过敏性炎症的发生。LTRA在儿童过敏性疾病的治疗中广泛应用,但仍存在质疑与挑战。因此,中国鼻病研究协作组召集国内中青年鼻科专家,制订了LTRA治疗儿童变应性鼻炎专家共识,旨在指导儿童变应性鼻炎临床诊疗工作。目前国内外指南均推荐LTRA作为儿童变应性鼻炎治疗的一线药物。儿童对孟鲁司特一般耐受性良好,总体不良反应发生率与安慰剂相似,对神经精神影响的研究尚无统一意见,临床医师应意识到神经精神事件的潜在风险,在开具相应处方时注意权衡利弊。

腺样体肥大患儿腺样体组织中半胱氨酰白三烯受体1的表达及其影响因素

目的分析半胱氨酰白三烯受体1(CysLTR1)在腺样体肥大(adenoid hypertrophy,AH)患儿腺样体组织中的表达特点,探究CysLTR1在AH形成中的作用机制及CysLTR1表达的影响因素。方法选取2020年10月1日—2021年10月1日在威海市立医院耳鼻咽喉科行腺样体切除术患儿71例,对其切除标本行CysLTR1免疫组化染色,根据染色结果分为CysLTR1高表达组及低表达组。收集两组患儿性别、年龄、腺样体肥大程度、有无变应性鼻炎、有无其他合并症(分泌性中耳炎、慢性鼻窦炎、呼吸睡眠暂停综合征)等资料并进行比较,通过多因素logistic回归分析影响AH患儿CysLTR1表达的危险因素。结果免疫组化染色结果显示,CysLTR1在71例AH患儿腺样体组织中均有表达,高表达组患儿的腺样体肥大程度、有无变应性鼻炎及有无其他合并症与低表达组相比差异有显著性(χ^(2)=9.003~49.196,P<0.05)。多因素logistic回归分析显示,重度腺样体肥大、变应性鼻炎以及有其他合并症均为影响AH患儿CysLTR1表达的独立危险因素(P<0.05)。结论CysLTR1在AH患儿腺样体组织中表达与腺样体肥大程度、有无变应性鼻炎及其他合并症相关,且上述3指标为CysLTR1高表达的独立危险因素。

慢性鼻窦炎患儿血清LTB4、NLRC4水平变化及对术后复发的预测价值

目的探究慢性鼻窦炎(CRS)患儿血清白三烯B4(LTB4)、Nod样受体家族蛋白4(NLRC4)水平变化及其临床意义。方法2020年1月至2021年10月选取接受鼻窦内窥镜治疗的184例CRS患儿(CRS组),根据术后3个月预后分为复发组与未复发组。另以同期100例体检健康儿童作为对照(NC)组。酶联免疫吸附法检测血清LTB4、NLRC4水平,比较各组血清LTB4、NLRC4水平。分析CRS组患儿在术前以及术后1周、4周、8周视觉模拟量表(VAS)评分、Lund-Kennedy评分及血清LTB4、NLRC4水平变化。采用Pearson法分析血清LTB4与NLRC4水平的相关性。多因素logistic回归分析CRS患儿术后复发的可能影响因素。受试者工作特征(ROC)曲线分析术前血清LTB4、NLRC4对术后复发的预测价值。结果CRS组患儿血清LTB4水平为(62.85±13.17)pg/mL、NLRC4水平为(759.82±108.46)pg/mL,NC组的血清LTB4水平为(17.43±4.08)pg/mL、NLRC4水平为(203.75±36.93)pg/mL,两组比较差异均有统计学意义(P<0.001)。相关性分析显示,CRS组血清LTB4与NLRC4水平呈正相关性(r=0.638,P<0.001)。血清LTB4水平、NLRC4水平与CRS患儿年龄、性别、是否伴有鼻息肉无关(P>0.05)。术前、术后1周、术后4周、术后8周VAS评分、Lund-Kennedy评分及血清LTB4、NLRC4水平依次下降(P<0.05)。复发组术前血清LTB4水平为(77.62±15.85)pg/mL、NLRC4水平为(860.39±126.92)pg/mL,显著高于未复发组的(57.78±12.25)pg/mL、(725.32±102.13)pg/mL,差异有统计学意义(P<0.001)。多因素logistic回归分析结果显示,术前血清LTB4、NLRC4水平均是CRS患儿复发的危险因素(OR=2.114,95%CI=1.129~3.958;OR=1.883,95%CI=1.190~2.979)(P<0.05或0.01)。NLRC4、LTB4及二者联合预测术后复发的曲线下面积(AUC)分别为0.839、0.824、0.913。结论慢性鼻窦炎患儿血清LTB4、NLRC4表达水平升高,且与预后密切相关,两者联合有望成为慢性鼻窦炎术后复发的早期预测指标。

清热健脾利湿方联合常规西药治疗脾虚湿蕴型慢性湿疹临床研究

目的:观察清热健脾利湿方联合常规西药治疗脾虚湿蕴型慢性湿疹的临床疗效。方法:选取96例慢性湿疹患者,按随机数字表法分为对照组和研究组各48例。对照组给予常规西药治疗,研究组在对照组基础上给予清热健脾利湿方治疗。评价2组临床疗效,统计复发率,比较2组治疗前后中医证候评分、瘙痒严重程度评估量表(12-PSS)评分、湿疹面积及严重程度指数(EASI)评分,检测2组皮肤屏障功能指标、免疫功能及炎症因子水平。结果:研究组总有效率为97.92%,高于对照组83.33%(P<0.05)。研究组复发率为7.69%,低于对照组66.67%(P<0.05)。治疗后,2组中医证候评分较治疗前降低(P<0.05),且研究组中医证候评分低于对照组(P<0.05)。治疗后,2组12-PSS、EASI评分较治疗前降低(P<0.05),且研究组12-PSS、EASI评分低于对照组(P<0.05)。治疗后,2组经皮水分丢失(TEWL)较治疗前降低,研究组TEWL低于对照组(P<0.05);2组角质层含水量、皮脂含量较治疗前升高,研究组角质层含水量、皮脂含量高于对照组(P<0.05)。治疗后,2组Th1/Th2、白细胞介素-6受体(IL-6R)、白细胞三烯B4 (LTB4)、Fas配体(Fas-L)水平较治疗前降低(P<0.05);且研究组Th1/Th2、IL-6R、LTB4、Fas-L水平低于对照组(P<0.05)。结论:清热健脾利湿方联合常规西药治疗脾虚湿蕴证慢性湿疹患者,可改善皮肤屏障功能,调节外周血细胞免疫平衡,降低炎症因子水平,改善瘙痒程度,缓解病情,提升临床疗效,降低复发率。

白三烯受体拮抗剂对哮喘患者生存质量和气道炎症的作用

目的探讨白三烯受体拮抗剂-扎鲁司特对成人哮喘患者生存质量和气道炎症的作用。方法40例哮喘患者随机分为治疗组和对照组各20例。治疗组口服扎鲁司特。对照组不用安可来。服药前及4周后采用成人哮喘生存质量评估表评估。并测定治疗前后气道炎症各指标水平。结果口服扎鲁司特4周后生存质量各因子分及总均分均有显著改善;气道炎症各指标均明显低于治疗前及对照组(P均<0.05)。结论扎鲁司特能改善哮喘患者的生存质量、抑制哮喘的气道炎症。

哮喘儿童白三烯受体调节剂临床疗效与白三烯C4合成酶及5-脂氧化酶基因的相关性

目的探讨白三烯C4合成酶(LTC4S)与5-脂氧化酶(ALOX5)基因多态性与白三烯受体拮抗剂临床疗效的关系。方法 2011年6月至2013年6月门诊72例中度持续哮喘患儿分为两组,分别予吸入型糖皮质激素激素(ICS)、ICS联合白三烯受体拮抗剂(LTRA)治疗12周,然后交叉治疗12周;采用聚合酶链反应—限制性片段长度多态性方法(PCRRFLP),对LTC4S RS730012、ALOX5 RS2115819位点进行基因分型;分析患儿治疗前后肺功能及儿童哮喘控制测试问卷(C-ACT)评分与基因多态性的关系。结果经ICS联合LTRA治疗后,LTC4S RS730012基因组中的A/C、C/C基因型患儿的75%肺活量时的用力呼气流速(FEF75)改善率显著优于A/A型,差异均有统计学意义(P<0.01);A/A基因型患儿在治疗前后改善情况的差异无统计学意义。ICS联合LTRA治疗前后,ALOX5 RS2115819基因组中的不同基因型患儿间的肺功能指标差异无统计学意义(P>0.05)。结论 LTC4S RS730012不同基因型患儿在哮喘治疗后小气道功能改善有差异,与LTRA相关。

半胱氨酰白三烯受体2多克隆抗体制备及其鉴定

目的:制备半胱氨酰白三烯受体2(CysLT2)多克隆抗体,并鉴定其免疫学特性及应用。方法:以KLH偶联的CysLT2受体多肽免疫家兔制备抗体,用间接ELISA法测定抗体效价,以抗原阻断法测定抗体敏感性及特异性;同时,以新制备的抗体进行Western blot和免疫组化,检测CysLT2受体的组织表达。结果:ELISA测定显示,获得的家兔抗CysLT2受体抗体的效价大于1/1 047 296,对CysLT2受体的特异性强,对CysLT1受体和GPR17基本无交叉反应。Western blot结果显示,CysLT2受体在大鼠、小鼠肾、脑和肺中有较高的表达,其分子量在40 kD左右。免疫组化结果表明,CysLT2受体主要表达在大鼠神经元,也表达在部分星形胶质细胞。结论:制备的CysLT2受体多克隆抗体具有高效价和高特异性,能满足Western blot和免疫组化检测的要求。

白三烯受体基因mRNA表达水平与儿童哮喘的关系

目的研究白三烯受体基因mRNA在儿童外周血白细胞中的表达;对比白三烯受体基因mRNA在哮喘组和健康对照组之间表达水平的差异;研究轻、中、重度哮喘患儿白三烯受体基因mRNA表达水平是否存在差异;探讨性别和年龄因素对哮喘组白三烯受体基因mRNA表达水平的影响。方法应用逆转录聚合酶链式反应(RT-PCR)技术,引入内参β-actin,应用电泳凝胶定位分析仪,1D凝胶分析软件,对比并定量分析CysLT1-Receptor和CysLT2-Receptor基因mRNA在哮喘组和对照组之间的表达差异,对所得数据进行统计学分析、处理和评价。结果在哮喘组及对照组中均可检测到CysLT1-Receptor和CysLT2-Receptor基因mRNA的表达;哮喘组白三烯受体基因mRNA的表达显著高于对照组,差异有显著性(P均<0.01);轻、中、重度哮喘患儿CysLT1-Receptor和CysLT2-Receptor基因mRNA表达水平差异无显著性;性别、年龄因素对哮喘组白三烯受体基因mRNA表达无影响(P均>0.05)。结论CysLT1-Receptor和CysLT2-Receptor基因在儿童外周血白细胞中存在表达,其mRNA表达水平在哮喘组显著增高;性别和年龄因素对哮喘组白三烯受体基因mRNA的表达无影响。

白三烯受体拮抗剂对哮喘小鼠的气道炎症及肺内一氧化氮合酶的影响

目的 :研究白三烯受体拮抗剂对哮喘气道炎症过程及肺内一氧化氮合酶 (NOS)的影响。方法 :C57BL/6J小鼠分为 3组 :哮喘组 (7只 ) ,正常对照组 (6只 ) ,扎鲁司特 (白三烯受体拮抗剂 )组 (7只 )。建立小鼠哮喘模型 ,给予口服扎鲁司特 40mg·kg 1 ·d 1 ,共 5d ,观察支气管肺泡灌洗液 (BALF)中白细胞总数 ,嗜酸细胞百分比 (EOS % ) ,血涂片 ,骨髓片中EOS % ,并用免疫组化的方法观察使用扎鲁司特后诱生型一氧化氮合酶 (iNOS)、内皮型一氧化氮合酶 (eNOS)的表达情况。结果 :哮喘组BALF中白细胞总数 [(1 3 .9± 0 .8)× 1 0 6 ml 1 ]、EOS % [(47.75± 1 3 .0 9) % ]显著高于正常对照组 (P <0 .0 0 1 ) ,正常对照组相应数值分别为 (1 .9± 0 .5)× 1 0 6 ml 1 和 (0 .2± 0 .0 1 ) % ,口服扎鲁司特后BALF中白细胞总数 [(1 .3± 0 .4)× 1 0 6 ml 1 ]、EOS % [(1 .33± 1 .0 7) % ]显著低于哮喘组 (P <0 .0 0 1 ) ,哮喘组激发后第一天血涂片中EOS % [(1 8.75± 8.54) % ]显著高于对照组 [(1 .5± 1 .0 ) % ,P <0 .0 0 1 ] ,扎鲁司特组在激发后第 1天血涂片中EOS %则较正常对照组明显下降 [(6 .95± 3 .83) % ] ,哮喘组骨髓片中EOS % [(1 3 .5±3 .9) % ]显著高于正常对照组 [(2 .5± 2 .9) % ] ,而扎鲁司特组 [(

孟鲁司特治疗病毒感染婴幼儿喘息的临床疗效评价

目的观察孟鲁司特治疗病毒感染婴幼儿喘息的临床疗效。方法将79例呼吸道病毒检测阳性的喘息患儿分为研究组和对照组,对照组41例患儿给予常规治疗,研究组38例患儿在对照组常规治疗基础上口服孟鲁司特,4mg/次,每晚顿服,连用7d。观察两组患儿临床疗效和研究组患儿的不良反应情况。结果两组患儿在咳喘消失时间、啰音消失时间和吸氧、全身性激素及雾化吸入使用率方面差异均有统计学意义(P<0.05);研究组患儿均未发现明显不良反应。结论孟鲁司特治疗病毒感染婴幼儿喘息的疗效确切,可减少其他对症治疗的使用,不良反应少,值得临床推广应用。

白三烯受体拮抗剂ONO-1078对内皮素-1诱导的大鼠局灶性脑缺血的保护作用

目的 观察白三烯受体拮抗剂ONO 10 78对内皮素 1诱导的大鼠局灶性脑缺血的保护作用。方法 向大脑中动脉附近微量缓慢注射内皮素 1( 12 0pmol,6 μL ,>6min) ,诱导大鼠局灶性脑缺血模型 ,在注射内皮素 1前 1hipONO 10 78( 0 1mg·kg- 1 )。观察神经症状、脑水肿程度、脑梗死体积、纹状体和皮层的存活神经元数的变化。结果脑内微量注射内皮素 1引起动物出现明显神经症状、脑梗死、脑水肿及皮层和纹状体的存活神经元减少。预先ipONO 10 78显著抑制脑水肿 ,减小脑梗死体积 ,增加纹状体和皮层的存活神经元数 ,可减轻神经症状 ,但无显著意义。结论 ONO 10 78对内皮素 1诱导的脑缺血损伤有保护作用 ,白三烯参与了脑缺血后的组织损伤过程。

半胱氨酰白三烯受体1拮抗剂普鲁司特调节SK-N-SH细胞分化

目的:观察半胱氨酰白三烯受体激动剂LTD4以及受体1(CysLT1)拮抗剂普鲁司特对人神经母细胞瘤细胞株SK-N-SH细胞分化的影响。方法:以维A酸为阳性对照,观察LTD4、普鲁司特、LTD4+普鲁司特诱导SK-N-SH细胞形态学变化;用免疫印迹法观察SK-N-SH细胞CysLT1和CysLT2受体的表达;用免疫荧光法观察神经元分化标记物微管相关蛋白(MAP-2)的表达。结果:免疫印迹显示,SK-N-SH表达CysLT1受体和CysLT2受体,CysLT2受体表达较多。形态学结果显示,维A酸、普鲁司特、LTD4+普鲁司特诱导SK-N-SH细胞发生形态学改变,表现为胞体变小,有明显的突起生长;而LTD4无明显作用。免疫荧光结果显示,在对照组和普鲁司特组MAP-2主要分布于胞体;在维甲酸组MAP-2除了分布于胞体外,还分布于突起。普鲁司特增加MAP-2阳性细胞数。结论:CysLT1受体拮抗剂普鲁司特参与SK-N-SH细胞分化的调节。