Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing

Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.

Resolvins抗炎镇痛研究进展

Resolvins是来源于ω-3多不饱和脂肪酸(polyunsaturated fatty acids,PUFA)、经相应酶催化合成的一种脂类介质,由于其独特的抗炎镇痛作用而被大家所关注。本文就近年来关于Resolvins的合成、代谢、生物学功能及其与炎症和疼痛疾患的关系等进行综述。

Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids(ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins astargets in inflammatory diseases and cancers.

IL-23和RvE1在桥本甲状腺炎炎症调控中的潜在作用

桥本甲状腺炎是一种常见的自身免疫性疾病,其特征是甲状腺特异性自身抗体的存在,目前其发病机制尚未完全明确,但与遗传、环境及表观遗传因素的相互作用有关。疾病的发展主要涉及细胞免疫和体液免疫,经常出现T细胞和B细胞的炎症浸润。在组织病理学上,IL-23是一种重要的细胞因子,在先天免疫和适应性免疫中发挥作用,是促进多种靶器官炎症反应的关键因子。Resolvin E1(RvE1)是一种内源性脂质介质,源于二十碳五烯酸(EPA),在许多疾病模型中显示出保护作用。综述了IL-23和RvE1在桥本甲状腺炎炎症调控中的潜在作用,以期开发更精准的治疗方法,改善患者生活质量,降低相关并发症的风险。

Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells

Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.

High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic postischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord

Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

n-3脂肪酸代谢产物抗炎作用的研究进展

炎症反应是机体正常组织对感染和损伤的应答,然而过度的炎症反应往往会引起急性和慢性疾病的发生.最近研究发现,由n-3多不饱和脂肪酸二十碳五烯酸和二十二碳六烯酸代谢产生的resolvins和protectins两类化合物,具有很强的抗炎和炎症修复活性.综述了resolvins和protectin D1的来源、抗炎作用和抗炎机制,为进一步开展n-3多不饱和脂肪酸及其代谢产物的抗炎作用研究、为炎症的防治提供新的思路.

A defect in the activities of △~6 and △~5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.

Resolvin D_2对刀豆素A诱导的小鼠肝损伤的保护作用及机制的研究

目的探讨Resolvin D2对刀豆素A(ConA)诱导的肝损伤的保护作用及作用机制。方法实验小鼠随机分为三组,每组8只。正常小鼠对照组,ConA诱导的肝损伤模型组,ConA诱导肝损伤小鼠+Resolvin D2治疗组。测定血中的AST、ALT含量;病理切片观察各组肝组织病理变化;ELISA法测定各组小鼠血中细胞因子TNF-α、IFN-γ的水平;RT-PCR测定各组肝组织细胞因子TNF-α、IFN-γ的含量。结果 ConA模型组的转氨酶(AST、ALT)及细胞因子(TNF-α、IFN-γ)水平显著高于其他两组,差异具有统计学意义(P<0.05);而正常组与治疗组之间差异无统计学意义(P>0.05);病理切片显示,进行过Resolvin D2预处理的小鼠肝脏组织坏死程度较ConA模型组明显减轻。结论 Resolvin D2能够明显减轻肝脏损伤,这种保护作用是通过抑制细胞因子TNF-α、IFN-γ的释放取得的。

<i>In Vitro</i>and <i>in Vivo</i>Anti-Inflammatory Effect of a Biotechnologically Modified Borage Seed Extract: Evidence for Lipid Pro-Resolving Mediators’ Implication in the Enhancement of Psoriatic and Atopic Dermatitis Lesions

Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1β, IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the in vitro co-culture model used. Introduced in formulation, borage seed oil aminopropanediol amides significantly reduced the clinical manifestations of psoriasis and atopic dermatitis. Conclusion: Our in vitro and in vivo study clearly showed the anti-inflammatory activity of borage seed oil aminopropanediol amides and emphasized the putative role of pro-resolving lipid mediators in the treatment of atopic dermatitis, psoriasis or other inflammation-induced skin diseases.

ChemR23及其配体研究进展

近年来,肿瘤迁移与微环境的关系已经成为研究热点。众多研究表明通过调节肿瘤微环境可抑制肿瘤的迁移。新近研究表明,类趋化因子受体CMLR1(又称为ChemR23)及其配体介导的信号转导和细胞间相互作用在肿瘤微环境的调节中发挥重要作用。因此,ChemR23及其信号通路可能成为肿瘤防治的一个新靶点。

脂氧素A4、保护素D1、ResolvinD1抑制多种激动剂引起的NFκB的活化

目的探讨脂质小分子脂氧素A4(LXA4)、保护素D1(ProD1)、ResolvinD1(RvD1)对核因子κB(NFκB)活性的影响及作用机制。方法稳定表达NFκB荧光素酶报告基因的中国仓鼠卵巢细胞分别由100 nmol/L LXA4、ProD1、RvD1预处理30 min后,细胞被激动剂LPS、HSP70、HMGB1或S100A4刺激。通过检测荧光素酶活性以评价脂质小分子对激动剂激活NFκB活性的作用。细胞培养上清中TNFα的含量由ELISA检测,胞核中NFκB的含量由Western印迹检测。结果 LPS、HSP70、HMGB1和S100A4显著上调NFκB的活性,增加细胞分泌的TNFα的量。LXA4、ProD1、RvD1显著抑制NFκB激活,降低细胞分泌的TNFα含量,减少NFκB的入核。结论 LXA4、ProD1、RvD1显著抑制多种激动剂活化NFκB,其作用机制可能与其能降低NFκB的入核有关,这几个脂质小分子在研制新型抗炎药物方面具有进一步开发和研究的潜力。

ResolvinE1对高危角膜移植免疫排斥反应的抑制作用

背景 以往防治角膜移植术后排斥反应的药物存在诱发局部或全身不良反应的风险，研究表明resolvinE1（RvE1）能够调节辅助性T细胞1（Th1）型免疫反应，但其对高危角膜移植术后的植片排斥反应有无抑制作用尚不清楚。目的观察高危角膜移植动物模型局部应用RvE1对植片免疫排斥反应的抑制作用。方法 以BALB/c小鼠为受体、C57BL/6小鼠为供体行角膜移植术。采用随机数字表法将90只BALB/c小鼠随机分成异体角膜移植组、异体角膜移植＋RvE1组和自体角膜移植组，每组各30只。BALB/c小鼠右眼先用缝线法刺激2周以建立高危角膜移植眼模型，然后行穿透角膜移植术。异体角膜移植组和异体角膜移植＋RvE1组小鼠右眼行异体角膜移植，自体角膜移植组小鼠将右眼角膜植片旋转180°后缝合于植床上。异体角膜移植组及自体角膜移植组小鼠术后每日用生理盐水10 μl结膜下注射1次，异体角膜移植＋RvE1组小鼠术后同法注射终质量浓度为0.1 μg/μl的RvE1 10 μl，连续7 d。术后裂隙灯显微镜下观察小鼠角膜植片反应并对其排斥反应进行评分。术后21 d处死各组小鼠各20只，收集小鼠术眼角膜、眼球和术眼侧颈部淋巴结，采用苏木精－伊红染色法观察各组小鼠角膜植片的组织病理学变化；采用免疫组织化学法检测术眼角膜中CD4及γ干扰素（IFN-γ）的表达；采用流式细胞术检测术眼侧颈部淋巴结淋巴细胞中Th1细胞（CD3＋CD8a－IFN-γ＋）比例；采用荧光定量PCR法检测Th1细胞相关因子白细胞介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）、IFN-γ及T-bet mRNA的相对表达水平。结果 异体角膜移植＋RvE1组小鼠角膜植片存活时间为（28.5±1.7）d，明显长于异体角膜移植组的（14.0±1.6）d，差异有统计学意义（t＝4.14，P〈0.001），自体角膜移植组小鼠植片在术后50 d存活率为100%。苏木精－伊红染色显示，异体角膜移植＋RvE1组和自体角膜移植组小鼠角膜植片水肿及炎性细胞浸润程度均轻于异体角膜移植组。免疫组织化学法检测显示，各组角膜全层均有CD4表达，而IFN-γ主要表达于角膜上皮层，异体角膜移植组小鼠角膜组织中CD4和IFN-γ阳性细胞数均明显多于异体角膜移植＋RvE1组和自体角膜移植组。流式细胞术检测显示，异体角膜移植＋RvE1组和自体角膜移植组小鼠淋巴细胞中Th1细胞比例分别为（1.07±0.25）%和（0.85±0.12）%，明显低于异体角膜移植组的（1.56±0.20）%，差异均有统计学意义（均P〈0.05）。荧光定量PCR检测显示，异体角膜移植组小鼠角膜中IL-2、TNF-α、IFN-γ及T-bet mRNA的相对表达量明显高于异体角膜移植＋RvE1组和自体角膜移植组，差异均有统计学意义（均P〈0.05）。结论 RvE1可抑制小鼠高危角膜移植排斥反应，作用机制可能与其下调角膜植片和淋巴细胞中Th1细胞及相关细胞因子的表达有关。

血清炎性细胞因子和Resolvin D1浓度与结肠癌病理分期的关系

目的 探讨结肠癌患者体内炎性细胞因子水平和Resolvin D1(RvD1)浓度及其与肿瘤病理分期的关系.方法 收集复旦大学附属中山医院普通外科2016年1—12月期间的50例结肠癌住院患者的临床资料和入院时的全血标本5 ml(结肠癌组);同时,入组同期健康志愿者50例(健康志愿组).结肠癌组的入组标准:结肠癌术前肠镜和病理诊断明确,无近期肠内肠外营养支持治疗及应用口服营养制剂,年龄不超过85岁,术前评估无手术禁忌证,无服用鱼油相关制剂的病史,并排除术前行放疗化疗者.健康志愿者组入组标准:无恶性肿瘤病史、本院体检中心检查无脏器器质性病变、检测指标在正常参考值范围以及未服用鱼油相关制剂、且年龄不超过85周岁者.采用化学发光免疫分析仪检测血清炎性因子(IL-1β、IL-6、IL-10及TNF-α)浓度,采用酶联免疫吸附法检测血清RvD1浓度.比较两组的炎性因子和RvD1浓度水平并分析其与本组结肠癌患者TNM分期的关系.结果 两组受试者在年龄、性别以及营养学相关指标上,差异无统计学意义(均P>0.05).健康志愿者组中男性31例,女性19例,年龄(61.8±11.6)岁;结肠癌组中男性23例,女性27例,年龄(65.4±12.4)岁,参照第7版美国癌症联合会TNM分期标准:Ⅰ期10例,Ⅱ期13例,Ⅲ期17例,Ⅳ期10例.与健康志愿者组比较,结肠癌组受试者血清中的IL-1β[(3.89±0.24)×10^3μg/L比(1.55± 0.37)×10^3μg/L,t=37.52,P<0.01]、IL-6[(129.14±3.07)×10^3μg/L比(51.46±3.14)×10^3μg/L,t=125.08, P<0.01]、IL-10[(100.59±8.69)×10^3μg/L 比(27.57±4.77)×10^3μg/L,t=52.09,P<0.01]及 TNF-α [(114.31±4.43)×10^3μg/L比(41.04±5.27)×10^3μg/L,t=75.25,P<0.01]浓度均较高,而RvD1浓度相对较低[(34.19±1.93)×10^3μg/L比(77.76±1.02)×10^3μg/L,t=140.56,P<0.01],差异均有统计学意义.将结肠癌组患者根据TNM分期进行亚组分析,IL-6、IL-1β、IL-10及TNF-α浓度随TNM分期的进展有逐渐升高趋势(P<0.01),至Ⅲ期时IL-6、IL-1β、IL-10浓度最高,至Ⅳ期时TNF-α浓度最高;而RvD1浓度随TNM分期的进展有逐渐降低趋势(P<0.01).结论 与健康志愿者相比,结肠癌患者血液内炎性细胞因子水平明显升高,RvD1水平明显降低,两者均与肿瘤分期进展有关.

来源于n-3多不饱和脂肪酸的新型抗炎介质Resolvin，docosatriene及neuroprotectin

研究表明，n-3多不饱和脂肪酸能调节免疫，缓解急性和慢性炎症疾病。传统观点认为n-3多不饱和脂肪酸的抗炎机制是通过竞争环氧酶和脂氧酶从而减少来源于花生四烯酸（AA）的促炎性介质的生成，或通过影响酶与细胞因子的基因表达，抑制促炎症因子产生、调节黏附分子表达来调节免疫功能。但近期研究发现，二十碳五烯酸（EPA）与二十二碳六烯酸（DHA）可在代谢过程中产生一类新型的脂质介质（Resolvin、docosatriene），其在炎症衰退阶段的渗出物中可被检测到，这些代谢中间物都具有潜在的抗炎及免疫调节活性，从而在新的方面揭示了n-3多不饱和脂肪酸发挥抗炎及免疫调节活性的分子机制。

Resolvin D1对脂多糖诱导小鼠急性肺损伤的保护作用

目的 探讨Resolvin D1（RvD1）对脂多糖（LPS）诱导小鼠急性肺损伤的治疗作用。方法体重20~25 g的BALB/c小鼠21只随机分3组,1对照组,气管内滴注PBS;2LPS模型组,气管内滴注LPS（100μg/60μl）,作用6 h;3RvD1组,在气管内滴注LPS 30 min前给予RvD1（600 ng/100μl/只）尾静脉注射,LPS作用6小时。观察各组小鼠肺组织病理组织学变化,肺泡灌洗液（BALF）中炎症细胞总数及中性粒细胞变化,BALF中促炎性细胞因子IL-6及抗炎性细胞因子IL-10含量变化及肺组织内丙二醛（MDA）的浓度。结果 在LPS刺激的小鼠中,组织病理学显示大量的炎性细胞浸润,肺泡内出血,水肿,肺组织结构明显被破坏,BALF中细胞总数、中性粒细胞及肺组织内MDA含量明显增高,BALF中促炎性细胞因子IL-6显著升高。而以RvD1预处理小鼠明显抑制LPS诱发的上述改变,同时中抗炎因子IL-10显著升高。结论 RvD1可能通过重建抗炎反应和炎症反应的平衡对急性肺损伤发挥保护作用。

Resolvin因子治疗眼科疾病的实验研究进展

Resolvin是一类来源于ω3多不饱和脂肪酸的内源性促进炎症消退的介质。目前研究发现，Resolvin可抑制T淋巴细胞和中性粒细胞的浸润，下调炎症相关因子的表达，调节免疫功能，并在多种眼科动物模型中显示出可预防治疗干眼症、角膜炎、葡萄膜炎等眼科疾病。本文对Resolvin与眼科相关炎症性疾病的研究进行了探讨。

自身免疫性甲状腺炎患者血清resolvin E1水平及临床意义

目的探讨自身免疫性甲状腺炎(autoimmune thyroiditis,AIT)患者血清resolvin E1(RvE1)水平及临床意义。方法将2019年10月至2021年10月海安市人民医院收治的92例AIT患者作为AIT组,同期体检的60例健康人员作为对照组。双电化学发光法测定检测游离三碘甲状腺原氨酸(free thyronine3,FT3)、游离甲状腺素(free thyroxine4,FT4)、抗甲状腺过氧化物酶抗体(thyroid peroxidase antibody,TPOAb)和甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)水平;双抗体夹心酶联免疫吸附法检测血清RvE1,γ-干扰素(interferon-γ,IFN-γ)和白细胞介素-35(interleukin-35,IL-35)水平,并进行组间比较。应用Pearson相关分析分析血清RvE1与Thl/Th2、TPOAb、TGAb、IFN-γ、IL-35的相关性,受试者工作特性曲线(receiver operator characteristic curve,ROC)评估血清RvE对AIT的诊断价值,多因素Logistic回归分析探讨AIT患者影响因素。结果AIT组患者血清RvE1、IL-35水平明显低于对照组,[pg/mL:(23.24±4.20)比(29.66±5.69),ng/mL:(44.20±8.65)比(62.24±10.14),t值分别为7.99、11.73,P值均<0.05]。AIT组患者Thl/Th2、IFN-γ、TPOAb、TGAb水平明显高于对照组[(16.20±5.20)比(5.10±1.15),pg/mL:(7.88±1.63)比(4.21±0.28),IU/mL:(587.54±120.20)比(5.14±1.20),(380.20±80.41)比(3.20±0.36),t值分别为16.26、17.26、36.37、34.99,P值均<0.05]。Pearson相关性分析显示:AIT患者血清RvE1水平与Thl/Th2、TPOAb、TGAb、IFN-γ水平呈负相关(r值分别为-0.42,-0.36,-0.31,-0.46,P值均<0.05),与IL-35水平呈正相关(r=0.37,P<0.05)。ROC曲线结果显示血清RvE1诊断AIT的曲线下面积(area under curve,AUC)为0.810,截断值为25.63 pg/mL,敏感度及特异度分别为80.63%、85.69%。多因素Logistic回归分析得出血清RvE1、IFN-γ、IL-35、Thl/Th2均为AIT发生的危险因素(P<0.05)。结论AIT患者血清RvE1水平降低,且血清RvE1水平与自身相关抗体、免疫功能及炎症指标密切相关。血清RvE1对AIT患者具有较好的诊断价值,有望作为临床评估AIT发生的有效指标。

Resolvin D1预处理通过NF-κB及焦亡影响失血性休克肝损伤

目的探讨Resolvin D1预处理对失血性休克小鼠肝脏损伤的保护作用及可能机制。方法 30只雄性C57BL/6小鼠,随机分成Sham组、HS/R组及Resolvin D1组,每组10只。血生化检测各组小鼠肝脏功能;HE染色观察肝脏形态学变化;ELISA检测炎症因子水平;Western Blot检测焦亡相关蛋白NLRP3、IL-1β、Caspase1及TLR4和NF-κB信号通路相关蛋白p-NF-κB p65和IκBα表达情况。结果 Resolvin D1对失血性休克小鼠肝损伤具有显著的改善作用,Resolvin D1组小鼠相对于HS/R组肝脏功能异常减轻;肝脏损伤病理结构改善;炎症因子表达显著降低;焦亡相关蛋白NLRP3、IL-1β、Caspase1的表达均显著降低;且Resolvin D1抑制pNF-κB p65蛋白表达水平及IκBα蛋白降解。结论 Resolvin D1能够改善失血性休克小鼠肝损伤肝细胞焦亡,其作用机制可能与抑制NF-κB信号通路有关。