κ-阿片受体激动剂U50488H通过调节巨噬细胞极化减轻体外循环致大鼠急性肺损伤的研究

目的探讨κ-阿片受体(KOR)激动剂U50488H是否通过调节巨噬细胞极化减轻体外循环(CPB)引发的大鼠急性肺损伤(ALI)。方法将24只成年雄性清洁级SD大鼠(50~450 g)随机分为Sham组(假手术)、CPB组(CPB)和U50488H组(KOR激动剂+CPB),每组8只。U50488H组于CPB前30 min静脉注射1.5 mg/kg U50488H。分别于CPB后0、1、2 h行动脉血气分析,计算肺泡-动脉氧分压差(A-aDO_(2))和呼吸指数(RI)。3组大鼠均在停CPB后2 h处死,取完整右肺下叶。采用重力法测定血管外肺水(EVLW),采用苏木精-伊红(HE)染色观察肺组织形态学变化。采用酶联免疫吸附试验(ELISA)检测血浆酯多糖(LPS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-4(IL-4)含量。采用免疫荧光法测定大鼠肺组织iNOS和CD206水平。结果与Sham组比较,CPB组大鼠EVLW和TNF-a、血浆IL-6水平及肺组织iNOS表达增高,血浆IL-4水平和肺组织CD206表达降低,差异有统计学意义(P<0.05)。CPB后0、1、2 h,CPB组的A-aDO_(2)和RI、LPS高于Sham组,U50488H组的A-aDO_(2)和RI、LPS低于CPB组,差异有统计学意义(P<0.05)。CPB组大鼠出现严重肺损伤和肺泡内充血/出血,并伴有广泛的炎症细胞浸润,U50488H组肺损伤显著减轻。结论KOR激动剂U50488H可促进CPB后大鼠肺巨噬细胞向M2表型极化,减轻炎症反应,增加抗炎因子释放,进而减少CPB后ALI的发生。

δ-Opioid receptor as a potential therapeutic target for ischemic stroke

Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.

Opiate-induced constipation related to activation of small intestine opioid μ2-receptors

AIM:To investigate the role of opioid μ-receptor subtype in opiate-induced constipation (OIC).METHODS:The effect of loperamide on intestinal transit was investigated in mice.Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension.The ileum strips were precontracted with 1 μmol/L acetylcholine (ACh).Then,decrease in muscle tone (relaxation) was characterized after cumulative administration of 0.1-10 μmol/L loperamide into the organ bath,for a concentration-dependent study.Specific blockers or antagonists were used for pretreatment to compare the changes in loperamide-induced relaxation.RESULTS:In addition to the delay in intestinal transit,loperamide produced a marked relaxation in isolated ileum precontracted with ACh,in a dose-dependent manner.This relaxation was abolished by cyprodime,a selective opioid μ-receptor antagonist,but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors.Also,treatment with opioid μ-1 receptor agonist failed to modify the muscle tone.Moreover,the relaxation by loperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K + (K ATP) channels,and by protein kinase A (PKA) inhibitor,but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP).CONCLUSION:Loperamide induces intestinal relaxation by activation of opioid μ-2 receptors via the cAMPPKA pathway to open K ATP channels,relates to OIC.

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral <i>µ</i>-opioid receptors

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats;to determine whether tolerance develops to these responses;and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous injection of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent injections of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first injection of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

Expression of mu-opioid receptors in human chronic inflamed knee joint synovium tissue

Objective: To examine the changes of mu-opioid receptors (MORs) expression in human chronic inflamed knee joint synovium tissue. Methods:Knee joint synovium tissues were taken from 21 patients with chronic arthritis (inflamed group) and 6 fresh bodies with normal knee joints (control group). And the expression of MORs was detected by using immunohistochemistry. flow cytometry(FCM) and reverse-transcription polymerase chain reaction (RT-PCR). Results: The expression of MORs in the inflamed group was significantly higher than that in the normal group by using the 3 techniques(P<0. 05). Conclusion: Chronic inflammation enhances the up-regulation of MORs in human knee joint synovium tissue.

Determination of structure-activity relationships between fentanyl analogs and human μ-opioid receptors based on active binding site models

Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.

MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.

Human μ-opioid receptor overexpressed in Sf9 insect cells functionally coupled to endogenous G_(i/o) proteins

Human μ-opioid receptor （HμOR） with a tag of six consecutive histidines at its carboxyl terminus had been expressed in recombinant baculovirus infected Sf9 insect cells.The maximal binding capacity for the [3H] diprenorphine and [3H]ohmefentanyl （Ohm） were 9.1± 0.7 and 6.52±0.23 nmol/g protein, respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by μ-selective agonists [D-Ala2], N-methylPhe4, glyol5]enkephalin （DAGO）, Ohm, and morphine, but neither by δ nor by K selective agonist. Na+ （100 mM） and GTP （50 μM） could reduce HμOR agonists etorphine and Ohm affinity binding to the overexpressed HμOR. μ-selective agonists DAGO and Ohm effectively stimulated [35S]GTPγS binding (EC50 = 2.7nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin （PTX）. These results demonstrated that HμOR overexpressed in Sf9 insect cells functionally coupled to endogenous Gi/o proteins.

Molecular characterization and functional expression of opioid receptor-libe_1 receptor

The opioid receptor-libel receptor (ORL), an orphan receptor whose human and murine complementary DNAs,has been characterized recently. ORL transcripts are particularly abundant in the central nervous system. We demonstrated that ORL expressed in human neuroblastoma SK-N-SH and SH-SY5Y cell lines by radioligand binding assay, reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis in the present study. Stimulation with ORL1 specific agonist, nociceptin/orphanin Fo, increased [34S]GTPrγS binding to SK-N-SH cell membranes (EC50 = 14 ±0.45 nM), and attenuated forskolin-stimulated accumulation of cellular cAMP (EC50= 0.80 ±0.45 nM, indicative that activation of ORL1 activates G proteins and inhibits adenylyl cyclase. Activation of ORL1 receptor was also accessed using CHO:hORL1 cell line by microphysiometer. Treatment of nociceptin/orphanin FQ increased extracellular acidification rate significantly.

Nε-(carboxymethyl)lysine promotes lipid uptake of macrophage via cluster of differentiation 36 and receptor for advanced glycation end products

BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.

Immunohistochemical identification of dynorphin A and Kappa opioid receptor-1 in the digestive system of scallop Chlamys farreri

Little is known about the roles of dynorphin and Kappa opioid receptor(KOR) in mollusks. In this study, we aim to determine the distribution of dynorphin A and KOR-1 in the digestive system of the scallop Chlamys farreri. Using immunohistochemical staining, we confirmed the expression of dynorphin A and KOR-1 in the digestive system of C. farreri. Dynorphin A immunopositive cells were identified in intestine and hepatopancreas. In intestine, small and spherical dynorphin A immunopositive cells(4–9 μm in diameter) were scattered among the long columnar epithelial cells(ECs). In hepatopancreas, cells containing masses(5–14 μm in diameter) of dynorphin A immunopositive products were observed in epithelium of acinis. These immunopositive cells may be synthetic and/or secretory cells of dynorphin A. Dynorphin A immunoreactive products were commonly observed in epithelium and connective tissue(CT) of labial palps, mouth labia and stomach, which presented in forms of grains, fibers or flakes. KOR-1 immunoreactive material was observed in ECs and CTs of labial palps, mouth labia and stomach, intestine and hepatopancreas. The distribution of both dynorphin A and KOR-1 in the digestive organs suggests an involvement of dynorphin via KOR-1 in the functional regulation of the digestive system of C. farreri.

Thienorphine induces analgesia by binding κ -and δ-, or by partially binding μ-opioid receptor,thus further regulating cAMP-PKA activity

OBJECTIVE Thienorphine,a new oripavine derivative,has shown to possess stronger antinociceptive effects and better oral bioavailability compared to buprenorphine.The present study examines the effect of thienorphine on c AMP-dependent protein kinase A(PKA) activity in CHO cells expressing μ-,κ-,δ-and ORL1 receptors.In addition,we further examined its analgesic effect in vivo.METHODS The effect of thienorphine on cA MP-dependent PKA redistribution and cA MP inhibition were analyzed in CHO-PKAcatEGFP cells.PKA redistribution assays in CHO-PKAcatEGFP cells stably expressing μ-,κ-,δ-and ORL1 receptors were analyzed by high-throughput screening system to elucidate the efficacy of agonists or antagonists on opioid receptors.Moroever,the antinociceptive effects of thienorphine in vivo were examined using hot plate test.RESULTS Briefly,the maximum inhibition of thienorphine on PKA activity was about 36%,100%,100%and 12% in CHO-μ/κ/δ/ORL1-PKAcatE GFP cel s,respectively.In addition,thienorphine concentrationdependently inhibited the PKA activity with EC50 value of(22.7±18.1) nmol·L^(-1) in CHO-κ-PKAcatE GFP cels and(12.4±7.7) nmol·L^(-1) in CHO-δ-PKAcatE GFP cells.Thienorphine induced approximately 50%antinociceptive effect in mice lacking μ receptors compared to their wild-type controls(P<0.05).Also,the κ and δ selective antagonist nor-binaltorphimine,naltrindole decreased approximately 50%-60% in % MPE of theinorphine in μ-KO mice,respectively.The ORL1 receptor selective antagonist J113397 had no effect in %MPE of theinorphine in μ-KO mice.CONCLUSION Thienorphine induces analgesia through bindingκ-and δ-,or by partially binding μ-opioid receptor,thus further regulating the cAMP-PKA activity.Therefore,thienorphine may be used in acute or chronic pain with minimal addictive potential.

Effects of Peripherally Acting Opioid Ligands on Central Opioid Receptors and <i>β</i>-Endorphin Release in Stressed Rats

Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β-endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ-opioid system, but suppression of peripheral MOR activity induces activation of the central μ-opioid system, the interaction of which can be modulated by stress.

Functional expression of opioid receptor-like receptorand its endogenous specific agonist nociceptin/orphanin FQ during mouse embryogenesis

Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-PCR in mouse brain of day 8 embryo (E8)and the expression continued afterwards. Northern blotanalysis revealed abundant expression of ORL1 at postnatal day 1 (P1) and N/OFQ at E17 and P1 in the brain butnone was detected in other embryonic tissues. The presence of functional ORL1 in mouse embryonic brain wasalso confirmed by specific binding of [3H] N/OFQ (kd=1.3±0.5 nM and Bmax = 72±9 fmol/mg protein) as wellas by N/OFQ-stimulated G protein activation.

EFFECT OF ELECTROACUPUNCTURE ON THE IMMUNOREACTIVITY OF FOCAL CUTANEOUS μ-OPIOID RECEPTOR IMMUNOREACTION-POSITIVE FIBERS IN ADJUVANT ARTHRITIC RATS

客观：学习 -opioid 的效果在煽动性的皮肤织物和 electroacupuncture (EA ) 的效果的受体(粗腐殖质) 表示在在助手的粗腐殖质积极纤维的热门免疫反应(红外) 关节炎(AA ) 老鼠。方法：48 只 SD 老鼠的一个总数被使随机化进控制(n =8 ) ，模型(n= 10 ) ， focus-side-EA (n = 10 ) ， non-acupoint-EA (n = 10 ) ，并且 healthy-side-EA (n = 10 ) 组。 AA 模型被完全的 Freund 的助手的下的注射建立( CFA ， 50 L )进左后部的 paw.EA ( 4-16 Hz ， 0.5-1.5 V )为 30 min 在焦点或健康方面和 non-acupoints 上被用于“ Huantiao ”( GB 30 )和“ Yanglingquan ”( GB 34 )。使用的 Non-acupoints 是二个地点 5 公里到健康方面上的 GB 30 和 GB 34。在焦点的真皮、下的纸巾的热门粗腐殖质红外积极的纤维与 immunohistochemical 方法被染色。疼痛的严厉被把测试弄弯的脚(anklejoint ) 检测。结果：与模型组相比，“弯曲脚的测试” 20 在 第9 和 第11 天( P0.05 )并且在 non-acupoint-EA 组在 focus-side-EA 组显著地减少了在上 第8 ， 第9 并且在 CFA ( P 0.05 )的注射以后的 11thd ，都显示双边的 GB 30 和 GB 34 和 non-acupoints 的那 EA 能减轻疼痛。从第 13 天在上，没有重要差别在 3 个 EA 组和模型组(P0.05 ) 之中在“弯曲脚的测试”被发现分数。与控制组比较，在焦点织物的粗腐殖质红外积极的神经纤维的区域价值在在在模型的焦点的粗腐殖质红外积极的神经纤维的 .The 区域价值组织的 3 个 EA 组( P0.05 )是显著地更高的， 3 个 EA 组在控制组( P0.05 )比那高重要。与模型组相比，区域在组和 healthy-side-EA 组显著地增加了的 focus-side-EA (P 0.05 ) 粗腐殖质红外积极的纤维珍视；当在 non-acupoint-EA 组和 healthy-side-EA 组的粗腐殖质红外积极的纤维的那些在 focus-side-EA 是比那显著地低的时，组( P 0.05 )，和没有重要差别在粗腐殖质红外积极的纤维( P0.05 )的区域在模型组， healthy-side-EA 组和 non-acupoint-EA 组之中被发现，在焦点方面上显示 acupoints 的 EA 的更强壮的效果。结论：GB 30 和 GB 34 的 EA 能减轻煽动性的疼痛和起来调整在在 AA 老鼠的焦点的皮纸巾的粗腐殖质红外积极的纤维的表示，施加反煽动性、止痛的效果。

Dopamine D₁- and D₂-Receptors in Immunostimulation under Activation of Mu-Opioid Receptors in Mice with Different Psychoemotional States

The purpose of the present study was to analyze the effect of activation of mu-opioid receptors (mu-OR) on the immune response under blockade of postsynaptic D1-and D2-receptors in mice of the C57BL/6J strain displaying either aggressive or depressive-like behaviors in the social conflict model. It is shown that activation of activation of mu-OR with a highly selective agonist DAGO (100 μg/kg) increased significantly IgM-immune response not only in C57BL/6J mice with an unchanged psychoemotional state but also in mice displaying aggressive or depressive-like behaviors in the social stress model (10 days of agonistic confrontations). Selective blockade of DA receptors of the D1-type with SCH-23390 (1.0 mg/kg with DAGO administration) caused a more pronounced elevation of IgM-immune response than DAGO alone while DAGO effect was completely blocked by prior administration of D2-receptor antagonist haloperidol (1.0 mg/kg). At the same time, both SCH-23390 and haloperidol prevented the immune response increase induced by DAGO injection in mice engaged in aggressive or depressive-like behaviors. Thus, in animals not subjected to social stress DAGO-induced immunostimulation is provided only by D2-receptors, whereas in animals with altered psychoemotional state mu-opioid immunostimulation is mediated by both types of DA receptors—D1 and D2. These data provide evidence for different impacts of the main subtypes of DA receptors in the mediation of immunomodulating effects of mu-opioid system under normal and stressful conditions.

纳布啡在尿毒症瘙痒小鼠模型中的作用以及对IL-10和IL-31的影响

目的探讨纳布啡在尿毒症瘙痒小鼠模型中的作用以及对IL-10和IL-31的影响。方法将C57BL/6J小鼠分为3组,分别为对照组、模型组和纳布啡组,每组20只。纳布啡组静脉注射纳布啡0.6 mg/kg,对照组和模型组注射同体积0.9%氯化钠溶液。进行小鼠瘙痒行为学观察;HE染色观察小鼠皮肤病理改变;ELISA法检测血清中IL-10和IL-31;Western blot实验检测组织中IL-10、IL-31、FoxP3、CD80、CD163和iNOS的表达;Real-time PCR检测免疫细胞标志物。结果1~21 d,模型组和纳布啡组小鼠搔抓次数明显高于对照组(P<0.05),第14天和第21天,纳布啡组小鼠搔抓次数显著低于模型组(P<0.05);对照组皮肤组织病例尚未出现炎症细胞因子浸润和皮肤的改变。模型组皮肤组织可见大量炎症细胞,主要为嗜酸性粒细胞、淋巴细胞;与模型组对比,纳布啡组炎症细胞的浸润明显减少;与对照组相比,模型组小鼠血清中和组织中IL-10的表达以及蛋白表达明显降低(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中IL-10的表达以及蛋白表达显著升高(P<0.05);与对照组相比,模型组小鼠血清中和组织中IL-31的表达以及蛋白表达明显升高(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中IL-31的表达以及蛋白表达显著降低(P<0.05);对照组、模型组、纳布啡组中FoxP3、CD80和CD163蛋白和mRNA表达对比无显著性差异(P>0.05),与对照组相比,模型组小鼠血清中和组织中iNOS蛋白和mRNA的表达升高(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中iNOS蛋白和mRNA表达显低(P<0.05)。结论纳布啡对小鼠尿毒症瘙痒有明显的抑制作用,能够增加抗炎IL-10水平,降低IL-31,也能够降低少部分免疫细胞标志物的表达。

桥本甲状腺炎合并甲状腺乳头状癌患者中Toll样受体3和核转录因子-κB的表达及相关性分析

目的分析桥本甲状腺炎(Hashimoto thyroiditis,HT)合并甲状腺乳头状癌(PTC)患者Toll样受体3(toll-like receptor 3,TLR3)和核转录因子-κB(nuclear transcription factor-κB,NF-κB)表达及相关性。方法收取邯郸市中心医院2020年3月~2022年3月收治的130例行手术切除的甲状腺标本,其中正常甲状腺组织标本43例,HT标本47例,HT合并PTC标本40例,分析TLR3和NF-κB在正常甲状腺组织、HT组、HT合并PTC组中的表达,分析HT合并PTC组中TLR3和NF-κB表达与临床病理参数关系,Pearson相关性分析TLR3和NF-κB的关系。结果TLR3在正常甲状腺组织、HT组、HT合并PTC组中的阳性表达率分别为0(0/43)、80.85%(38/47)、90.00%(36/40);NF-κB在以上三组中的阳性表达率分别为0(0/43)、68.09%(32/47)、85.00%(34/40)。TLR3和NF-κB在HT组、HT合并PTC组中的阳性表达率均高于正常甲状腺组织(P<0.05),TLR3和NF-κB表达与性别、年龄、HT合并PTC病理学特征、病灶类型、淋巴结转移、甲状腺包膜侵犯差异比较均无统计学意义(P均>0.05)。TLR3和NF-κB呈显著正相关(r=0.589,P<0.05)。结论TLR3和NF-κB在HT合并PTC组织中的阳性率高于正常甲状腺组织,且二者表达呈正相关。

A non-opioid pathway for dynorphin-caused spinal cord injury in rats

Intrathecal injection of dynorphin into rats via subarachnoid catheter induces damage to spinal cord tissue and motor function. Injection of the kappa opioid receptor antagonist nor-binaltorphine, or the excitatory amino acid N-methyl-D-aspartate receptor antagonist MK-801 into rats alleviated the pathological changes of dynorphin-caused spinal cord tissue injury and reduced the acid phosphatase activity in the spinal cord. The experimental findings indicate that there are opioid and non-opioid pathways for dynorphin-induced spinal cord injury, and that the non-opioid receptor pathway may be mediated by the excitatory amino acid N-methyl-D-aspartate receptor.