馮永民，陳秋萍，黃柳濤，潘慶軍，劉華鋒

(廣東醫(yī)科大學(xué)附屬醫(yī)院，廣東湛江 524001)

活動(dòng)性系統(tǒng)性紅斑狼瘡患者外周血嗜堿性粒細(xì)胞CD62L、BAFF和CD40L表達(dá)變化及意義

馮永民，陳秋萍，黃柳濤，潘慶軍，劉華鋒

(廣東醫(yī)科大學(xué)附屬醫(yī)院，廣東湛江 524001)

目的 探討活動(dòng)性系統(tǒng)性紅斑狼瘡(SLE)患者外周血嗜堿性粒細(xì)胞淋巴歸巢受體(CD62L)、B淋巴細(xì)胞活化刺激因子(BAFF和CD40L)表達(dá)變化及意義。方法 選取SLE患者57例，根據(jù)SLEDAI評(píng)分將SLE患者分為活動(dòng)組(SLEDAI評(píng)分≥10分)29例和非活動(dòng)組(SLEDAI評(píng)分<10分)28例，選取同期20例查體健康者作為對(duì)照組，應(yīng)用流式細(xì)胞術(shù)檢測(cè)SLE患者和正常人外周血CD62L、BAFF和CD40L表達(dá)，并采用Spearman法分析其與血清Anti-dsDNA水平的相關(guān)性。結(jié)果 活動(dòng)組與非活動(dòng)組外周血CD62L表達(dá)水平均高于對(duì)照組(P均<0.05)，且活動(dòng)組高于非活動(dòng)組(P<0.05)?；顒?dòng)組外周血BAFF和CD40L表達(dá)水平均高于對(duì)照組和非活動(dòng)組(P均<0.05)；而非活動(dòng)組與對(duì)照組BAFF和CD40L表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)。SLE患者外周血嗜堿性粒細(xì)胞CD62L和CD40L表達(dá)與血清Anti-dsDNA抗體水平均呈正相關(guān)(r分別為0.34、0.36，P均<0.05)；而外周血嗜堿性粒細(xì)胞BAFF表達(dá)與血清Anti-dsDNA抗體水平無(wú)關(guān)(r=0.26，P=0.14)。結(jié)論 活動(dòng)性SLE患者外周血CD62L、BAFF和CD40L表達(dá)升高，嗜堿性粒細(xì)胞可能通過(guò)CD62L介導(dǎo)向次級(jí)淋巴器官遷移，通過(guò)BAFF和CD40L活化自身反應(yīng)性B淋巴細(xì)胞而產(chǎn)生多種自身抗體,進(jìn)而參與SLE的發(fā)病。

系統(tǒng)性紅斑狼瘡；嗜堿性粒細(xì)胞；嗜堿性粒細(xì)胞淋巴歸巢受體；B淋巴細(xì)胞活化刺激因子

系統(tǒng)性紅斑狼瘡(SLE)是一種多因素參與、累及多系統(tǒng)、多臟器的高度異質(zhì)性的自身免疫性疾病，以產(chǎn)生多種高滴度自身抗體為顯著特點(diǎn)。目前SLE機(jī)體免疫功能異常的機(jī)制尚未完全明了，Th1/Th2失衡[1～3]、多克隆自身反應(yīng)性B細(xì)胞的過(guò)度活化并伴以免疫負(fù)調(diào)節(jié)機(jī)制的缺損導(dǎo)致多種自身抗體產(chǎn)生[4]，被認(rèn)為是SLE發(fā)病的重要機(jī)制。研究報(bào)道，嗜堿性粒細(xì)胞表面表達(dá)B淋巴細(xì)胞刺激因子(BAFF)[5]及CD40L[6]。BAFF在B淋巴細(xì)胞存活和分化中發(fā)揮重要作用。CD40L是B淋巴細(xì)胞活化的共刺激分子，能提供B細(xì)胞活化的第二信號(hào)。此外，有學(xué)者將嗜堿性粒細(xì)胞與B細(xì)胞共培養(yǎng)，發(fā)現(xiàn)培養(yǎng)上清中免疫球蛋白IgE及IgG4明顯增加[7]。嗜堿性粒細(xì)胞可通過(guò)增強(qiáng)Th2應(yīng)答而活化B細(xì)胞或直接作用于B細(xì)胞而產(chǎn)生多種自身抗體，可能參與多種自身免疫性疾病的發(fā)病過(guò)程。2012年5月，我們檢測(cè)了57例SLE患者外周血嗜堿性粒細(xì)胞CD62L、BAFF和CD40L表達(dá)，并探討其意義。

1 資料與方法

1.1 臨床資料 選取2012年5月～2013年3月廣東醫(yī)學(xué)院附屬醫(yī)院腎病內(nèi)科確診的57例SLE患者，男7例、女50例，均符合美國(guó)風(fēng)濕病學(xué)會(huì)1997推薦的SLE診斷標(biāo)準(zhǔn)。排除合并感染、過(guò)敏、合并其他自身免疫性疾病、腎功能受損(以血肌酐超過(guò)基礎(chǔ)值2倍以上)的患者。收集SLE患者的臨床資料和實(shí)驗(yàn)室檢查數(shù)據(jù)，并計(jì)算患者SLE活動(dòng)指數(shù)(SLEDAI),根據(jù)SLEDAI評(píng)分將SLE患者分為活動(dòng)組(SLEDAI評(píng)分≥10分)29例(男3例，女26例)和非活動(dòng)組(SLEDAI評(píng)分<10分)28例(男4例，女24例)，活動(dòng)組與非活動(dòng)組年齡分別為(26.8±10.1)、(31.6±8.7)歲。同時(shí)按照性別和年齡相匹配的原則選取健康志愿者20例(男4例，女16例)作為對(duì)照組，年齡(28.3±6.7)歲。

1.2 外周血嗜堿性粒細(xì)胞CD62L、BAFF和CD40L表達(dá)的檢測(cè)方法 采用流式細(xì)胞術(shù)。采集受試者清晨空腹外周靜脈血3 mL，EDTA抗凝。取流式上樣管進(jìn)行編號(hào)，每一例標(biāo)本分為3管，依次為A、B、C管。在每一流式上樣管內(nèi)加入4 mL現(xiàn)配的1×紅細(xì)胞裂解液，再加入200 μL EDTA抗凝外周靜脈血充分混勻，避光放置15 min。1 500 r/min(300 g)×6 min離心后棄上清液，加入細(xì)胞染色液2 mL，充分混勻，再次離心，去上清，加入細(xì)胞染色液100 μL重懸細(xì)胞。A 管為空白管，不加入任何抗體；B 管為同型對(duì)照管，加入與C管所加抗體等量的同種屬同型對(duì)照抗體；C管滴加熒光素標(biāo)記的鼠抗人相應(yīng)抗體各5 μL。各管均用震蕩器充分混勻，室溫避光孵育30 min。加染色液2 mL，離心，去上清，重復(fù)2次。滴加細(xì)胞染色液200 μL重懸細(xì)胞，流式檢測(cè)備用。加熒光標(biāo)記抗體及之后的操作均在避光下進(jìn)行。常規(guī)采用空白對(duì)照、同型對(duì)照試劑和熒光微球Flow Check對(duì)流式細(xì)胞儀進(jìn)行調(diào)控，以熒光微球上機(jī)調(diào)定熒光變異系數(shù)值小于4%；各熒光素之間熒光補(bǔ)償調(diào)至標(biāo)準(zhǔn)值范圍內(nèi)。根據(jù)前向散射角(FSC)和側(cè)向散射角(SSC)，對(duì)單個(gè)核細(xì)胞群進(jìn)行設(shè)門(mén)，以SSC/CD203c 標(biāo)記嗜堿性粒細(xì)胞。對(duì)熒光標(biāo)記的細(xì)胞進(jìn)行分析，以同型對(duì)照組為基準(zhǔn)設(shè)門(mén)，確定嗜堿性粒細(xì)胞陽(yáng)性表達(dá)位置。使用FCS Express軟件分析數(shù)據(jù),以特異性標(biāo)記物平均熒光強(qiáng)度(MFI)與相應(yīng)同型對(duì)照MFI的差值，代表相應(yīng)生物學(xué)指標(biāo)的相對(duì)表達(dá)水平。 Anti-dsDNA采用ELISA法檢測(cè)(上?？菩律锛夹g(shù)股份有限公司)。

2 結(jié)果

2.1 外周血嗜堿性粒細(xì)胞流式細(xì)胞術(shù)定位 外周血嗜堿性粒細(xì)胞主要分布于單個(gè)核細(xì)胞群，更接近于淋巴細(xì)胞群。

2.2 各組外周血CD62L表達(dá)比較 非活動(dòng)組、活動(dòng)組、對(duì)照組外周血CD62L表達(dá)水平分別為261.3(154.8，352.0)、322.5(279.0，444.4)、129.0(107.5，174.0)，三組間比較，P均<0.05。

2.3 各組外周血BAFF和CD40L表達(dá)比較 非活動(dòng)組、活動(dòng)組、對(duì)照組外周血BAFF表達(dá)水平分別為102.0(37.9，217.3)、220.5(99.2，280.6)、106.0(51.0，153.0)，CD40L表達(dá)水平分別為78.0(53.7，140.0)、146.0(109.5，240.5)、84.5(37.0，281.5)，活動(dòng)組與另外兩組BAFF和CD40L表達(dá)比較，P均<0.05；對(duì)照組與非活動(dòng)組BAFF和CD40L表達(dá)比較，P均>0.05。

2.4 外周血嗜堿性粒細(xì)胞CD62L、CD40L及BAFF表達(dá)與SLE患者血anti-dsDNA抗體水平的關(guān)系 SLE患者外周血嗜堿性粒細(xì)胞CD62L和CD40L表達(dá)與血清Anti-dsDNA抗體水平均呈線(xiàn)性正相關(guān)(r=0.340，P=0.015；r=0.360，P=0.017)；而外周血嗜堿性粒細(xì)胞BAFF表達(dá)與血清Anti-dsDNA抗體水平無(wú)線(xiàn)性相關(guān)關(guān)系(r=0.260，P=0.140)。

3 討論

SLE是典型的自身免疫性疾病，以自身反應(yīng)性T、B細(xì)胞異?；罨岸喾N自身抗體產(chǎn)生為特點(diǎn)，常伴有多個(gè)組織器官損傷。研究發(fā)現(xiàn)，嗜堿性粒細(xì)胞參與天然免疫、獲得性免疫、免疫平衡調(diào)節(jié)等[8]，但在SLE發(fā)病中的作用，至今少見(jiàn)文獻(xiàn)報(bào)道。嗜堿性粒細(xì)胞參與過(guò)敏反應(yīng)已被熟知[9]，近年有關(guān)嗜堿性粒細(xì)胞在天然免疫、獲得性免疫、免疫平衡調(diào)節(jié)等方面的研究取得較大進(jìn)展[8]。在免疫調(diào)節(jié)方面，嗜堿性粒細(xì)胞表面表達(dá)高水平的IgE受體FcεRI，通過(guò)與抗原特異IgE交聯(lián)，或其他的活化途徑，能產(chǎn)生Th2型細(xì)胞因子如IL-4和IL-13[10]。研究[11～13]發(fā)現(xiàn)，堿性粒細(xì)胞可通過(guò)MHC Ⅱ分子參與抗原提呈，在體內(nèi)介導(dǎo)Th0向Th2細(xì)胞分化[13,14]而增強(qiáng)體液免疫應(yīng)答[15]。Charles等[16]報(bào)道，蛋白酪氨酸激酶Lyn 缺陷(Lyn-/-)的老年小鼠外周血嗜堿性粒細(xì)胞能被自身反應(yīng)性免疫復(fù)合物(IgE-CICs)活化后高表達(dá)膜性BAFF。

本研究中我們以外周血嗜堿性粒細(xì)胞為研究對(duì)象，應(yīng)用流式細(xì)胞術(shù)檢測(cè)其CD62L、BAFF和CD40L表達(dá)，初步探討嗜堿性粒細(xì)胞在SLE發(fā)病中的作用。首先，我們應(yīng)用流式細(xì)胞術(shù)明確嗜堿性粒細(xì)胞在流式外周血白細(xì)胞散點(diǎn)圖中的位置，結(jié)果顯示，外周血嗜堿性粒細(xì)胞主要分布于流式細(xì)胞術(shù)血細(xì)胞散點(diǎn)圖中單個(gè)核細(xì)胞群，更接近于淋巴細(xì)胞群，與國(guó)外研究報(bào)道一致[17,18]。

文獻(xiàn)報(bào)道，嗜堿性粒細(xì)胞表達(dá)黏附分子CD62L，CD62L是一種淋巴歸巢受體[16,19]。Martin等[20]在乳腺瘤病毒感染的BALB/c小鼠淋巴結(jié)中發(fā)現(xiàn)明顯的樹(shù)突狀細(xì)胞浸潤(rùn)，而預(yù)先用anti-CD62L抗體處理后小鼠淋巴結(jié)浸潤(rùn)的樹(shù)突狀細(xì)胞明顯減少，此提示樹(shù)突狀細(xì)胞向淋巴結(jié)的遷移依賴(lài)于CD62L的作用。同樣，CD62L可介導(dǎo)淋巴細(xì)胞通過(guò)高靜脈內(nèi)皮細(xì)胞向次級(jí)淋巴組織器官遷移[21]。有研究報(bào)道，在以Th2應(yīng)答為主的Lyn-/-SLE樣小鼠外周血嗜堿性粒細(xì)胞CD62L表達(dá)上調(diào)，同時(shí)在其脾臟和淋巴結(jié)均可見(jiàn)嗜堿性粒細(xì)胞浸潤(rùn)[13]，提示CD62L可能介導(dǎo)外周血嗜堿性粒細(xì)胞向次級(jí)淋巴組織器官遷移。而本研究結(jié)果顯示，活動(dòng)性SLE患者嗜堿性粒細(xì)胞CD62L表達(dá)高于非活動(dòng)性SLE患者，提示外周血嗜堿性粒細(xì)胞CD62L表達(dá)與SLE病情活動(dòng)有關(guān)，且高表達(dá)CD62L的活動(dòng)性SLE患者嗜堿性粒細(xì)胞可能向次級(jí)淋巴細(xì)胞遷移。但基于倫理問(wèn)題，本研究未能在SLE患者次級(jí)淋巴器官中檢測(cè)嗜堿性粒細(xì)胞的浸潤(rùn)情況。此外，SLE患者外周血嗜堿性粒細(xì)胞CD62L表達(dá)高于正常人，且與血清抗-dsDNA抗體水平呈正相關(guān)，提示外周血嗜堿性粒細(xì)胞CD62L可能與SLE自身抗體的產(chǎn)生有關(guān)，參與SLE的病理生理過(guò)程。

自身抗體主要由SLE患者體內(nèi)自身反應(yīng)性B淋巴細(xì)胞異?；罨只癁闈{細(xì)胞而產(chǎn)生。文獻(xiàn)報(bào)道，嗜堿性粒細(xì)胞可延長(zhǎng)漿細(xì)胞的存活，促進(jìn)漿細(xì)胞產(chǎn)生更多免疫球蛋白IgG1及IgG2[22]。此外，有學(xué)者將嗜堿性粒細(xì)胞與B細(xì)胞體外共培養(yǎng)，發(fā)現(xiàn)培養(yǎng)上清中免疫球蛋白IgE及IgG4明顯增加[16]。研究報(bào)道，嗜堿性粒細(xì)胞表面表達(dá)BAFF[5]及CD40L[6]。過(guò)表達(dá)于樹(shù)突狀細(xì)胞的BAFF可促進(jìn)漿母細(xì)胞的存活和漿細(xì)胞分化[23]。Mackay等[24]研究發(fā)現(xiàn)，BAFF轉(zhuǎn)基因小鼠可出現(xiàn)B細(xì)胞功能失常而呈現(xiàn)SLE樣綜合征。CD40L是B淋巴細(xì)胞活化的共刺激分子，與表達(dá)于B淋巴細(xì)胞表面的CD40相互作用，可提供B細(xì)胞活化的第二信號(hào)。本研究結(jié)果顯示，活動(dòng)性SLE患者外周血嗜堿性粒細(xì)胞BAFF和CD40L表達(dá)均高于非活動(dòng)性SLE及正常人，提示嗜堿性粒細(xì)胞BAFF和CD40L表達(dá)與SLE病情活動(dòng)有關(guān)。最近，美國(guó)FDA批準(zhǔn)Belimumab用于SLE的治療，該藥主要靶向BAFF，療效顯著[25,26]。其機(jī)制除了抑制B淋巴細(xì)胞活化，有可能亦清除了部分表達(dá)BAFF的嗜堿性粒細(xì)胞，從而控制SLE活動(dòng)。此外，CD40L水平與血清抗-dsDNA抗體水平呈正相關(guān)，提示CD40L可能與自身抗體產(chǎn)生有關(guān)。因此，我們推測(cè)活動(dòng)性SLE外周血嗜堿性粒細(xì)胞由CD62L介導(dǎo)向次級(jí)淋巴組織器官遷移，一方面通過(guò)BAFF作用延長(zhǎng)自身反應(yīng)性B淋巴細(xì)胞的存活，一方面通過(guò)CD40L活化自身反應(yīng)性B淋巴細(xì)胞而產(chǎn)生多種自身抗體，從而參與SLE發(fā)病。

[1] Funauchi M, Ikoma S, Enomoto H, et al. Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus[J]. Scand J Rheumatol, 1998,27(3):219-224.

[2] Richaud-Patin Y, Alcocer-Varela J, Llorente L. High levels of TH2 cytokine gene expression in systemic lupus erythematosus[J]. Rev Invest Clin, 1995,47(4):267-272.

[3] Li WX, Chen GM, Yuan H, et al. Polymorphisms of the TIM-1 and TIM-3 genes are not associated with systemic lupus erythematosus in a Chinese population[J]. Mutagenesis, 2011,26(4):507-511.

[4] Sanz I, Lee FE. B cells as therapeutic targets in SLE[J]. Nat Rev Rheumatol, 2010,6(6):326-337.

[5] Chen K, Xu W, Wilson M, et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils[J]. Nat Immunol, 2009,10(8):889-898.

[6] Vishnevetsky D, Kiyanista VA, Gandhi PJ. CD40 ligand: a novel target in the fight against cardiovascular disease[J]. Ann Pharmacother, 2004,38(9):1500-1508.

[7] Yanagihara Y, Kajiwara K, Basaki Y, et al. Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation[J]. Clin Exp Immunol, 1998,111(1):136-143.

[8] Schneider E, Thieblemont N, De Moraes ML, et al. Basophils: new players in the cytokine network[J]. Eur Cytokine Netw, 2010,21(3):142-153.

[9] Javaloyes G, Goikoetxea MJ, Sanz ML, et al. Basophil activation test in the diagnosis of gadobutrol anaphylaxis[J]. Ann Allergy Asthma Immunol, 2012,108(4):286-287.

[10] Ben-Sasson SZ, Le Gros G, Conrad DH, et al. Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines[J]. Proc Natl Acad Sci U S A, 1990,87(4):1421-1425.

[11] Perrigoue JG, Saenz SA, Siracusa MC, et al. MHC class II-dependent basophil-CD4+T cell interactions promote T(H)2 cytokine-dependent immunity[J]. Nat Immunol, 2009,10(7):697-705.

[12] Yoshimoto T, Yasuda K, Tanaka H, et al. Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+T cells[J]. Nat Immunol, 2009,10(7):706-712.

[13] Sokol CL, Barton GM, Farr AG, et al. A mechanism for the initiation of allergen-induced T helper type 2 responses[J]. Nat Immunol, 2008,9(3):310-318.

[14] Charles N, Watford WT, Ramos HL, et al. Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation[J]. Immunity, 2009,30(4):533-543.

[15] Denzel A, Maus UA, Rodriguez Gomez M, et al. Basophils enhance immunological memory responses[J]. Nat Immunol, 2008,9(7):733-742.

[16] Charles N, Hardwick D, Daugas E, et al. Basophils and the T helper 2 environment can promote the development of lupus nephritis[J]. Nat Med, 2010,16(6):701-707.

[17] Chirumbolo S. State-of-the-art review about basophil research in immunology and allergy: is the time right to treat these cells with the respect they deserve [J]. Blood Transfus, 2012,10(2):148-164.

[18] Dijkstra D, Hennig C, Witte T, et al. Basophils from humans with systemic lupus erythematosus do not express MHC-Ⅱ[J]. Nat Med, 2012,18(4):488-489.

[19] Wimazal F, Ghannadan M, Muller MR, et al. Expression of homing receptors and related molecules on human mast cells and basophils: a comparative analysis using multi-color flow cytometry and toluidine blue/immunofluorescence staining techniques[J]. Tissue Antigens, 1999,54(5):499-507.

[20] Martin P, Ruiz SR, del Hoyo GM, et al. Dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment[J]. Blood, 2002,99(4):1282-1288.

[21] Girard JP, Springer TA. High endothelial venules (HEVs): specialized endothelium for lymphocyte migration[J]. Immunol Today, 1995,16(9):449-457.

[22] Rodriguez Gomez M, Talke Y, Goebel N, et al. Basophils support the survival of plasma cells in mice[J]. J Immunol, 2010,185(12):7180-7185.

[23] MacLennan I, Vinuesa C. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses[J]. Immunity, 2002,17(3):235-238.

[24] Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations[J]. J Exp Med, 1999,190(11):1697-1710.

[25] Kaveri SV, Mouthon L, Bayry J. Basophils and nephritis in lupus[J]. N Engl J Med, 2010,363(11):1080-1082.

[26] Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial[J]. Lancet, 2011,377(9767):721-731.

Expression changes of CD62L, BAFF and CD40L in basophils of patients with systemic lupus erythematosus

FENGYongmin,CHENQiuping,HUANGLiutao,PANQingjun,LIUHuafeng

(AffiliatedHospitalofGuangdongMedicalUniversity,Zhanjiang524001,China)

Objective To investigate expression changes of lymph homing receptor (CD62L) and B-lymphocyte activation factors (BAFF and CD40L) in peripheral blood basophils of patients with active systemic lupus erythematosus (SLE) and their significance. Methods Fifty-seven SLE patients were selected and were divided into the active group (SLEDAI score≥10,n=29) and inactive group (SLEDAI score <10,n=28) according to the SLEDAI score. Twenty healthy volunteers were selected as the control group. The levels of CD62L, BAFF and CD40L in the peripheral blood basophils were detected by flow cytometry and their correlations with the Serum anti-dsDNA levels were analyzed by Spearman correlation analysis. Results The expression of CD62L in peripheral blood basophils of the active group and inactive group was higher than that of the control group, and the active group was significantly higher than the inactive group (P<0.05). The expression of BAFF and CD40L in peripheral blood basophils of the active group was significantly higher than that of the inactive group and control group (allP<0.05), while there was no significant difference between inactive group and control group (P>0.05). Expression of CD62L and CD40L in the peripheral blood basophils was positively correlated with serum anti-dsDNA levels in SLE patients (r=0.34,r=0.36; allP<0.05). The expression of BAFF in peripheral blood basophils was not related with serum anti-dsDNA levels in SLE patients (r=0.26,P=0.14). Conclusions Expression of CD62L, BAFF and CD40L in basophils of patients with active SLE increases. CD62L may mediate the basophils migrating to the secondary lymph organs where the basophils could activate the self-reactive B-lymphocytes producing diverse antibodies through BAFF and CD40L to participate in the pathogenesis of SLE.

systemic lupus erythematosus; basophil; CD62L; B-lymphocyte activation factors

國(guó)家自然科學(xué)基金資助項(xiàng)目(81202346)；廣東省自然科學(xué)基金項(xiàng)目(S2012040006216)；廣東省醫(yī)學(xué)科學(xué)技術(shù)研究基金項(xiàng)目(A2015520)。

馮永民(1978-)，男，碩士，副主任醫(yī)師，主要研究方向?yàn)槊庖咝阅I小球疾病發(fā)病機(jī)制。E-mail:fymcqp@163.com

劉華鋒(1969-)，男，博士，教授，博士生導(dǎo)師，主要研究方向?yàn)槊庖咝阅I小球疾病發(fā)病機(jī)制。E-mail:hf-liu@263.net

10.3969/j.issn.1002-266X.2017.09.006

R593.24

A

1002-266X(2017)09-0020-04

2016-11-20)