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semaphorin 3a controls allergic and inflammatory responses in experimental allergic conjunctivitis

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International Journal of Ophthalmology(English edition) 2015年第1期8卷 1-10页

作者： Junmi Tanaka Hideo Tanaka Nobuhisa Mizuki Eiichi Nomura Norihiko Ito Naoko Nomura Masayuki Yamane Tomonobu Hida Yoshio Goshima Hiroshi Hatano Hisashi Nakagawa Department of Ophthalmology and Visual Science Graduate School of MedicineYokohama City University Department of Ophthalmology Graduate School of MedicineUniversity of Tokyo Department of Obstetrics and Gynecology School of MedicineKeio University Department of Environmental Immuno-Dermatology Graduate School of MedicineYokohama City University Hatano Eye Clinic 438-1 FujisawaFujisawa Kanagawaken 251-0052Japan Tokushima Eye Clinic 1-2-14 Fujimi-choHigashimurayamaTokyo 189-0024Japan

AIM: To assess the efficacy of topical semaphorin 3a(SEMA3a) in the treatment of allergic ***: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3a(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC ***: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

关键词： semaphorin 3a experimental allergic conjunctivitis eosinophil infiltration serum total Ig E cytokines instillation subconjunctival administration

Reduced expression of semaphorin 3a in osteoclasts causes lymphatic expansion in a Gorham-Stout disease(GSD)mouse model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 38-50页

作者： Dongfang ZHANG Hao XU Chi QIN Kangming CAI Jing ZHANG Xinqiu XIA Jingwen BI Li ZHANG Lianping XING Qianqian LIANG Wensheng WANG Laboratory of Molecular Medicine College of Life Science and State Key Laboratory of Cell Differentiation and RegulationHenan Normal UniversityXinxiang453007China Longhua Hospital&Spine Institute Shanghai University of Traditional Chinese MedicineShanghai200032China Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)Shanghai201203China Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochester14642USA

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow *** the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely *** this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3a(Sema3a),which is an osteoprotective factor involved in the lymphatic expansion of *** to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3a is low compared to that in *** the presence of recombinant Sema3a,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3a on LECs in *** an LEC-induced GSD mouse model,the effect of Sema3a was examined by injecting lentivirus-expressing Sema3a into the tibiae in *** found that the overexpression of Sema3a in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3a short hairpin RNA(shRNA)into the tibiae caused GSD-like *** staining further demonstrated that OCs decreased and osteocalcin increased after Sema3a lentiviral treatment,compared with the *** on the above results,we propose that reduced Sema3a in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3a represents a new approach for the treatment of GSD.

关键词： semaphorin 3a Gorham-Stout disease Osteoclast Osteolysis Lymphatic endothelial cell

Silicified collagen scaffold induces semaphorin 3a secretion by sensory nerves to improve in-situ bone regeneration

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Bioactive Materials 2022年第3期7卷 475-490页

作者： Yu-Xuan Ma Kai Jiao Qian-Qian Wan Jing Li Ming-Yi Liu Zi-Bin Zhang Wen Qin Kai-Yan Wang Ya-zhou Wang Franklin R.Tay Li-Na Niu State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi710032China Department of Neurobiology The Fourth Military Medical UniversityXi’anShaanxi710032China The Graduate School Augusta UniversityAugustaGA30912USA

Sensory nerves promote osteogenesis through the release of ***,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain *** present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of *** wound sites were accompanied by extensive nerve innervation and *** nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent *** of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3a)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling *** medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor *** effects were inhibited by the use of Sema3a neutralizing antibodies but not by Sema4D neutralizing *** of Sema3a in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3a promoted the silicon-induced *** of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3a production were identified in the DRG of rats that were implanted with silicified collagen *** findings support the role of silicon in inducing Sema3a production by sensory nerves,which,in turn,stimulates osteogenesis and *** together,silicon has therapeutic potential in orthopedic rehabilitation.

关键词： Distal femur defect Mechanistic target of rapamycin semaphorin 3a Sensory nerve Silicified collagen scaffolds

Sustained release of semaphorin 3a from a-tricalcium phosphate based cement composite contributes to osteoblastic differentiation of MC3T3-E1 cells

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Frontiers of Materials Science 2015年第3期9卷 282-292页

作者： Jin-Ning WANG Bin PI Peng WANG Xue-Feng LI Hui-Lin YANG Xue-Song ZHU Department of Orthopaedic Surgery The first Affiliated Hospital of Soochow University Suzhou 215006 China

The reinforcement of calcium phosphate materials with silk fibroin （SF） has been one of the strategies to overcome the brittleness. However, the lack of osteoinductivity may still restrict their further use. This study aimed to investigate the biocompatibility and osteogenesis capacity of a novel semaphorin 3a-loaded chitosan microspheres/SF/a-tricalcium phosphate composite （Sema3a CMs/SF/a-TCP） in vitro. Sema3a was first incorporated into CMs, and the Sema3a CMs/SF/a-TCP composite was then prepared. The morphology of the CMs was observed using SEM. The in vitro release kinetics, cytotoxicity, and cell compatibility were evaluated, and the real-time quantitative polymerase chain reaction （RT-qPCR） and activity of alkaline phosphatase （ALP） were used to evaluate the osteogenesis capacity of the composite. The in vitro release of Sema3a from the Sema3a CMs/SF/a-TCP composite showed a temporally controlled manner. The extract of the Sema3a CMs/SF/a-TCP composite presented no obvious side effect on the MC3T3-E1 cell proliferation, nor promote cell proliferation. The MC3T3-E1 cells were well-spread and presented an elongated shape on the Sema3a CMs/SF/a-TCP composite surface; the ALP activity and the osteogenic-related gene expression were higher than those seeded on the surface of the CMs/SF/a-TCP and SF/a-TCP composites. In conclusion, Sema3a CMslSF/a-TCP has excellent biocompatibility and contributes to the osteoblastic differentiation of MC3T3-E1 cells.

关键词： α-tricalcium phosphate (o-TCP) silk fibroin (SF) semaphorin 3a osteo-blastic differentiation MC3T3-EI cell

semaphorin 3a expression in spinal cord injured rats after olfactory ensheathing cell transplantation

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Neural Regeneration Research 2011年第10期6卷 756-761页

作者： Guoyu Wang Xijing He Puwei Yuan Haopeng Li Rui Chang Second Department of Orthopedics Second Hospital of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China

semaphorin 3a expression is thought to increase following spinal cord *** impact of olfactory ensheathing cell transplantation remains *** current study demonstrated that spinal cord hemorrhage,edema,degeneration,necrosis,cyst formation,proliferation of glial cells,regeneration of nerve fibers and various pathological reactions occurred following a simple cross-section of spinal cord *** of olfactory ensheathing cells was found to significantly relieve the pathological reactions in the spinal cord described above,decrease the extent of necrosis in damaged neurons and nerve fibers,and downregulate semaphorin 3a expression in the injured *** results confirmed that olfactory ensheathing cell transplantation plays a protective role on the injured spinal cord by reducing the expression of semaphorin 3a.

关键词： olfactory ensheathing cells cell transplantation spinal cord injury tissue pathology semaphorin 3a neural regeneration

semaphorin 3a在系统性红斑狼疮合并血小板减少患者中的水平及意义

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北京大学学报（医学版） 2020年第5期52卷 892-896页

作者：郭倩马晓旭高辉石连杰钟昱超谢琳峰邵苗张学武北京大学人民医院风湿免疫科北京100044 北京大学国际医院风湿免疫科北京102206

目的:通过测定血清semaphorin 3a(Sema3a)的水平,分析Sema3a与系统性红斑狼疮(systemic lupus erythematosus,SLE)血小板减少的相关性。方法:应用酶联免疫吸附法检测170例SLE患者、50例干燥综合征(Sjogren’s syndrome,SS)患者、19例脾功能亢进(hypersplenism,HS)患者及150例健康对照(healthy controls,HC)血清中Sema3a的水平,收集患者及健康对照的临床资料及实验室检查,实验室检查主要为患者的血常规及骨髓穿刺活检结果。根据是否合并血小板减少及血小板减少是否缓解,将SLE患者分为SLE合并血小板减少组(41例)、SLE合并血小板减少缓解组(28例)及SLE未合并血小板减少组(101例)。根据是否合并血小板减少,将SS患者分为SS合并血小板减少组(18例)及SS未合并血小板减少组(32例)。将28例进行骨髓穿刺活检的SLE患者,根据骨髓象结果从骨髓增生情况方面将其分为骨髓增生正常组(19例)和增生减低组(9例),从巨核细胞成熟方面将其分为有巨核细胞成熟障碍组(8)和无巨核细胞成熟障碍组(20例)。比较各组Sema3a水平差异,并分析各组患者血清Sema3a水平与血小板的相关性及不同骨髓象间血清Sema3a的水平。结果:(1)SLE患者血清Sema3a水平较HC显著降低[(3.84±2.76)μg/L vs.(6.96±2.62)μg/L,P3a水平亦较HC显著降低[(4.35±3.57)μg/L vs.(6.96±2.62)μg/L,P3a水平较HC也明显降低[(5.67±2.26)μg/L vs.(6.96±2.62)μg/L,P=0.041]。(2)SLE患者血清Sema3a水平较SS患者降低,但差异无统计学意义[(3.84±2.76)μg/L vs.(4.35±3.57)μg/L,P=0.282],SLE患者血清Sema3a水平与HS患者相比显著降低,差异有统计学意义[(3.84±2.76)μg/L vs.(5.67±2.26)μg/L,P=0.006]。(3)SLE合并血小板减少组Sema3a水平显著低于SLE合并血小板减少缓解组[(1.28±1.06)μg/L vs.(3.83±2.65)μg/L,P3.83±2.65)μg/L vs.(4.87±2.60)μg/L,P=0.123]。SLE合并血小板减少组患者Sema3a水平与SS合并血小板减少组患者相比降低,但差异无统计学意义[(1.28±1.06)μg/L vs.(1.68±1.11)μg/L,P=0.189]。(4)相关性分析显示SLE患者的Sema3a水平与血小板显著相关(r=0.600,P3a水平与血小板亦呈明显的正相关(r=0.573,P3a却没有表现出明显的相关性(P=0.393)。(5)血清Sema3a在骨髓增生正常和减低的SLE患者,及有和无巨核细胞成熟障碍的SLE患者中的水平差异无统计学意义(P>0.05)。结论:血清Sema3a在多种合并血小板减少的疾病中水平普遍下降,SLE患者血清Sema3a水平显著降低,并与血小板呈明显正相关,在SS患者中亦可得出类似结论,提示Sema3a与结缔组织病的血小板减少相关。

关键词： semaphorin 3a 红斑狼疮,系统性血小板减少

Interplay of neuropilin-1 and semaphorin 3a after partial hepatectomy in rats

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World Journal of Gastroenterology 2012年第36期18卷 5034-5041页

作者： Ling Fu Tsuneo Kitamura Kazuhisa Iwabuchi Syozo Ichinose Mitsuaki Yanagida Hideoki Ogawa Sumio Watanabe Toshihide Maruyama Masafumi Suyama Kenji Takamori Institute for Environmental and Gender Specific Medicine Juntendo University Graduate School of Medicine Urayasu 279-0021 Japan Department of Gastroenterology Juntendo University Urayasu Hospital Urayasu 279-0021 Japan Department of Gastroenterology Juntendo University School of Medicine Tokyo 113-8421 Japan

AIM： To elucidate the role of neuropilin-1 （Nrp-1） and semaphorin 3a （Sema3a） in sinusoidal remodeling dur- ing liver regeneration in rats. METHODS： Male Wistar/ST rats at 7 wk of age, weigh- ing about 200 g, were used for all animal experiments. In vivo, at 24, 48, 72, 96, 144 and 192 h after two- thirds partial hepatectomy （PHx）, the remnant livers were removed. Liver tissues were immunohistochemi- cally stained for Nrp-1, Sema3a and SE-1, a liver sinu- soidal endothelial cell （SEC） marker. Total RNA of the liver tissue was extracted and reversely transcribed into cDNA. The mRNA expression of Sema3a was ana- lyzed by quantitative real-time polymerase chain reac- tion and normalized to that of ribosomal protein $18. In vitro, SECs were isolated from rat liver and cultured in endothelial growth medium containing 20 ng/mL vascular endothelial cell growth factor. Migration of SECs in primary culture was assessed by cell transwell assay with or without recombinant Sema3a. Apoptotic cells were determined by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method. RESULTS： In vitro, immunohistochemistry study re- vealed that Sema3a and Nrp-1 were constitutively ex- pressed in hepatocytes and SECs, respectively, in normal rat liver tissues. Nrp-1 expression in SECs was quantified by the percentage of immunostained area with anti- Nrp-1 antibody in relation to the area stained with SE-1. Between 24 h and 96 h following resection of liver, Nrp-1 expression in SECs was transiently increased. Compared with the baseline （5.2% ± 0.1%）, Nrp-1 expression in SECs significantly increased at 24 h （17.3% ± 0.7%, P 〈 0.05）, 48 h （39.1% ± 0.6%, P 〈 0.01）, 72 h （46.9% ± 4.5%, P 〈 0.01） and 96 h （29.9% ±3.8%, P 〈 0.01） after PHx, then returned to the basal level at termination of liver regeneration. Interestingly, the expression of Sema3a was inversely associated with that of Nrp-1 in liver after PHx. Sema3a mRNA expres- sion was significantly

关键词： Neuropilin-1 semaphorin 3a Sinusoidal re-modeling Liver regeneration Two-thirds partial hepa-tectomy Angiogenesis Liver sinusoidal endothelial cells

semaphorin 3a对脂肪间充质干细胞成骨分化的作用及机制研究

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Semaphorin 3A对脂肪间充质干细胞成骨分化的作用及机制研究

作者：周宇超第四军医大学

学位级别：硕士

目前,牙槽骨缺损或骨量不足的患者,尤其是伴有2型糖尿病(Type 2 diabetes mellitus,T2DM)等骨代谢障碍的患者,种植体骨结合差、种植修复失败率高的问题已引起广泛关注。利用干细胞通过骨组织工程技术解决骨代谢障碍患者牙槽骨缺损问题... 详细信息

目前,牙槽骨缺损或骨量不足的患者,尤其是伴有2型糖尿病(Type 2 diabetes mellitus,T2DM)等骨代谢障碍的患者,种植体骨结合差、种植修复失败率高的问题已引起广泛关注。利用干细胞通过骨组织工程技术解决骨代谢障碍患者牙槽骨缺损问题、促进其种植体骨结合是近年来的研究热点。其中,脂肪间充质干细胞(Adipose-derived stem cells,ADSCs)以其来源丰富、易获取、不受伦理学制约等得天独厚的优点而成为该领域的“明星干细胞”。但有研究表明,受其固有属性影响,ADSCs倾向于成脂分化而成骨分化能力较弱。因此,提高ADSCs成骨分化能力是解决上述问题的关键。脑信号蛋白semaphorin 3a(Sema3a)参与并正向调控骨代谢平衡,能促进成骨细胞及其前体细胞(如ADSCs)成骨,是一种极具应用前景的骨保护因子。本研究利用Sema3a重组蛋白处理小鼠ADSCs,重点观察Sema3a促进ADSCs成骨分化的时间效应,并通过相关体外实验分析Notch信号通路在其中发挥的作用,以期探明Sema3a促进ADSCs成骨分化的可能机制,为其最终用于临床工作、改善上述患者群种植体骨结合状况提供科学研究基础。【目的及意义】通过观察Sema3a对ADSCs成骨分化的促进作用及其时间作用模式,并借助Notch信号通路特异性阻断剂γ-分泌酶抑制剂(Gamma-secretase inhibitor,GSI)分析Notch信号通路在其中所扮演的角色,探索Sema3a促进ADSCs成骨分化的可能机制,为其在口腔种植领域的临床应用提供实验依据。【方法】1.Ⅰ型胶原酶消化法分离、培养C57BL/6小鼠ADSCs,并通过形态学观察、多向分化诱导和表面分子标志物检测对分离培养的细胞进行鉴定。2.利用q PCR,Western Blot和免疫荧光染色等方法,观察Sema3a及其受体Nrp1(Neuropilin-1)在ADSCs成骨分化过程中的表达变化;利用q PCR检测成骨相关基因、茜素红染色检测钙结节形成、ALP染色检测ALP活性等方法,观察Sema3a对ADSCs成骨的促进作用,重点关注其时间作用模式以及Sema3a对ADSCs干性的改变和成骨分化的启动作用。3.用GSI阻断Notch信号通路后,通过q PCR和Western Blot检测其对ADSCs干性的影响;利用q PCR检测Notch信号通路相关分子在ADSCs成骨分化过程中的变化趋势,并通过q PCR检测成骨相关基因以及ALP染色检测ALP活性、天狼星红染色检测胶原分泌、茜素红染色检测钙结节形成等方法观察GSI作用下成骨诱导7,14和21d时的成骨效果。以q PCR和免疫荧光染色的方法观察Sema3a重组蛋白作用下,ADSCs对Notch信号通路相关分子表达的变化。成骨诱导过程中,联合应用Sema3a重组蛋白与GSI,观察成骨效果。【结果】1.成功获得具有多向分化潜能的ADSCs。***本身及其成骨分化全过程中均表达Sema3a及其受体Nrp1,且Sema3a在成骨初期表达明显上调,之后逐渐降低、于成骨末期恢复到初始水平;而Nrp1表达水平始终保持恒定。Sema3a重组蛋白能促进ADSCs的成骨分化,且Sema3a作用时间越长、作用阶段越早,作用效果越明显。Sema3a能直接降低ADSCs干性、启动生长培养基中的ADSCs成骨分化。***阻断ADSCs中Notch信号通路后,ADSCs中干性相关基因表达降低。ADSCs中表达的Notch信号通路相关分子主要有Notch2,Jagged2,Hes1;ADSCs成骨分化早期,上述各分子表达明显下调。在ADSCs成骨分化早期用GSI处理7d可以增强ADSCs成骨分化,延长处理时间至14-21d则抑制ADSCs成骨分化。***3a重组蛋白可以降低ADSCs对Notch信号通路相关分子的表达;同单独应用Sema3a或GSI处理相比,成骨初期同时用Sema3a重组蛋白和GSI进行干预,不能进一步促进ADSCs成骨分化。【结论】***3a及其受体参与ADSCs成骨分化的全过程,其促进作用在成骨分化早期尤为明显,这种作用甚至是启动性的。***3a对ADSCs成骨分化的促进作用可能是通过降低ADSCs中Notch信号,进而降低ADSCs干性而实现的。

关键词：脂肪间充质干细胞 semaphorin 3a Notch信号通路成骨分化口腔种植修复

semaphorin 3a与慢性肾脏病患者机体炎症状态和免疫功能的相关性研究

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Semaphorin 3A与慢性肾脏病患者机体炎症状态和免疫功能的相关性...

作者：史卓雅青海大学

学位级别：硕士

目的:信号素3a(semaphorin3a,Sema 3a)是一类调节细胞功能和形态的保守导向蛋白,可调控心脏、肺、肾脏、骨骼及神经系统的发育,在肾脏的肾小管上皮细胞和足细胞中稳定表达,并参与了多种肾脏疾病发生发展的病理生理过程。近年有研究表明,... 详细信息

目的:信号素3a(semaphorin3a,Sema 3a)是一类调节细胞功能和形态的保守导向蛋白,可调控心脏、肺、肾脏、骨骼及神经系统的发育,在肾脏的肾小管上皮细胞和足细胞中稳定表达,并参与了多种肾脏疾病发生发展的病理生理过程。近年有研究表明,Sema 3a可调控炎症因子和免疫细胞,在炎症及免疫反应中扮演重要角色。炎症和免疫反应在慢性肾脏病(Chronic Kidney Disease,CKD)发生发展过程中起了重要作用,但Sema 3a是否参与了这一过程,目前尚不清楚。因此,本研究旨在通过观察CKD患者血液、尿液中Sema 3a与体内炎症和免疫相关指标之间的关系,探讨Sema 3a与CKD患者机体炎症状态和免疫功能的相关性。方法:本研究以2020年12月1日到2021年11月30日于青海大学附属医院就诊的CKD患者120例为研究对象。将120例患者分为四组,1组:e GFR>60ml/(min·1.73㎡);2组:15 ml/(min·1.73㎡)3㎡);3组:e GFR≤15 ml/(min·1.73㎡)未透析组;4组:e GFR≤15 ml/(min·1.73㎡)血液透析组,每组30例患者。收集上述研究对象的一般资料、临床生化指标、炎性指标和免疫学指标。用ELISA方法检测血清中Sema 3a、CD4、CD8、TNF-α及尿液中Sema 3a,分析患者血清和尿液中Sema 3a与各炎性指标和免疫指标的相关性,探讨Sema 3a与CKD患者机体炎症状态和免疫功能的相关性。结果:本研究共收集2020年12月1日到2021年11月30日于青海大学附属医院就诊的CKD患者120例。1.随着肾功能进展,CKD患者血、尿中Sema 3a在四组间均呈现先增高、后降低趋势。1组血、尿Sema 3a最低,2组血、尿Sema 3a最高。与1组、3组、4组相比,2组血Sema 3a升高明显(p3a也较其他3组升高,但统计学分析无意义(p>0.05)。***患者的CRP、ESR、N%、NLR随着疾病进展逐渐升高(p3、4组,而CD4/CD8明显高于3、4组。(p3.将Sema 3a与炎症、免疫因子进行相关性分析,发现血Sema 3a与CRP、TNF-α、CD4、CD8呈正相关。(p3a随着肾功能减退呈现先增高、后降低趋势。随着肾功能损害加重,体内炎性反应程度也逐渐加重,但免疫功能逐渐下降。血Sema 3a与CRP、TNF-α、ESR、CD4、CD8呈正相关。

关键词：慢性肾脏病 semaphorin 3a 炎症状态免疫功能