作者單位:063001 河北 唐山,唐山市人民醫(yī)院兒科(楊振朋,李 敏,寇永妹,吳丙美,趙永生,李 丹),檢驗(yàn)科(李世龍)
楊振朋,李 敏,寇永妹,吳丙美,趙永生,李世龍,李 丹
舒利迭治療兒童哮喘的療效及對(duì)血PDGF、Eotaxin和IL-35的影響
作者單位:063001 河北 唐山,唐山市人民醫(yī)院兒科(楊振朋,李敏,寇永妹,吳丙美,趙永生,李丹),檢驗(yàn)科(李世龍)
楊振朋,李敏,寇永妹,吳丙美,趙永生,李世龍,李丹
[摘要]目的探討舒利迭治療兒童哮喘的臨床療效,觀(guān)察其對(duì)血清中血小板源生長(zhǎng)因子(PDGF)、嗜酸粒細(xì)胞趨化因子(Eotaxin)和白細(xì)胞介素-35(IL-35)的影響。方法選取我院收治的支氣管哮喘患兒206例,隨機(jī)分為兩組,對(duì)照組(103例)應(yīng)用輔舒酮治療,觀(guān)察組(103例)應(yīng)用舒利迭治療。分別檢測(cè)治療前后患兒血清中PDGF、Eotaxin和IL-35的表達(dá)水平。結(jié)果治療1個(gè)月后,觀(guān)察組的總有效率明顯高于對(duì)照組;治療后兩組患兒血清PDGF和Eotaxin的表達(dá)均下降,IL-35的表達(dá)上升,但是治療后觀(guān)察組上述3指標(biāo)的改善幅度明顯大于對(duì)照組(P<0.05)。結(jié)論舒利迭可以改善兒童哮喘的治療效果,有效調(diào)節(jié)血清PDGF、Eotaxin和IL-35的含量,優(yōu)化體液環(huán)境和細(xì)胞因子的平衡,臨床可以積極應(yīng)用。
[關(guān)鍵詞]兒童;哮喘;舒利迭;PDGF;Eotaxin;IL-35
支氣管哮喘(簡(jiǎn)稱(chēng)哮喘)是一種由多種炎性細(xì)胞參與的氣道慢性炎性疾病,以慢性嗜酸性炎性反應(yīng)、氣道高反應(yīng)性和氣道重塑性為特點(diǎn),目前已經(jīng)成為兒童慢性呼吸系統(tǒng)疾病中患病率最高的疾病之一,且呈現(xiàn)逐年上升的趨勢(shì)[1]。有研究顯示,在哮喘發(fā)病過(guò)程中,血清血小板源生長(zhǎng)因子(PDGF)、嗜酸粒細(xì)胞趨化因子(Eotaxin)的表達(dá)上升,白細(xì)胞介素-35(IL-35)的表達(dá)下降,啟動(dòng)機(jī)體內(nèi)環(huán)境中的瀑布效應(yīng),加速病變進(jìn)展[2-4]。舒利迭是沙美特羅/丙酸氟替卡松復(fù)方制劑,近來(lái)顯示其不僅控制哮喘的效果好,還對(duì)內(nèi)環(huán)境中相關(guān)的細(xì)胞因子有一定的調(diào)節(jié)作用[5]。本研究針對(duì)我院收治的哮喘患兒在常規(guī)治療基礎(chǔ)上,應(yīng)用舒利迭治療,觀(guān)察治療效果及對(duì)血清PDGF、Eotaxin和IL-35的影響,以期為臨床工作提供理論支持。
1資料與方法
1.1病例資料選擇我院2009年1月~2012年12月診治的支氣管哮喘的患兒作為研究對(duì)象,共206例,納入對(duì)象均符合中華醫(yī)學(xué)會(huì)兒科分會(huì)呼吸學(xué)組2003年修訂的兒童支氣管診斷標(biāo)準(zhǔn)[6],均與患兒監(jiān)護(hù)人簽定知情同意書(shū),并經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn)。排除標(biāo)準(zhǔn):(1)患兒監(jiān)護(hù)人不同意觀(guān)察的;(2)伴有先天性疾病的患兒;(3)過(guò)敏體質(zhì)的患兒?;純耗挲g5~14(8.8±3.3)歲,病程1~12(4.2±2.7)年。按患兒入院順序進(jìn)行排序,應(yīng)用隨機(jī)數(shù)字表法分為兩組,觀(guān)察組103例,年齡5~13(8.7±3.5)歲,病程1~11(4.3±2.4)年;對(duì)照組103例,年齡5~14(8.9±3.5)歲,病程1~12(4.0±2.7)年。兩組在常規(guī)資料的比較中無(wú)顯著差異,具有可比性。
1.2方法對(duì)照組在常規(guī)治療及護(hù)理基礎(chǔ)上,加用輔舒酮(葛蘭素史克公司,國(guó)藥準(zhǔn)字H20010389,每吸含丙酸氟替卡松125 μg),1吸/次,2次/d,療程1個(gè)月。觀(guān)察組在常規(guī)治療及護(hù)理基礎(chǔ)上,加用舒利迭50 μg/100 μg(葛蘭素史克公司,國(guó)藥準(zhǔn)字H20090561,每吸含沙美特羅50 μg,丙酸氟替卡松100 μg),1吸/次,2次/d,療程1個(gè)月。治療期間兩組患兒有急性哮喘癥狀時(shí),按需使用萬(wàn)托林氣霧劑。
1.3PDGF、Eotaxin和IL-35的檢測(cè)分別在治療前及治療1個(gè)月后,于清晨抽取患兒空腹靜脈血10 ml,離心后取血清,置于-20 ℃冰箱中保存,樣本均于抽血后的2 w內(nèi)集中檢測(cè)。PDGF、Eotaxin和IL-35的檢測(cè)應(yīng)用酶聯(lián)免疫吸附法(ELISA),試劑均購(gòu)自武漢博士德生物技術(shù)公司,全自動(dòng)酶免分析系統(tǒng)為T(mén)ECAN RMP200。操作均由同一主管檢驗(yàn)師完成,嚴(yán)格質(zhì)量控制。
1.4療效判斷顯效:哮喘的臨床癥狀完全緩解,偶有輕度發(fā)作但不需要用藥即可緩解,最大呼氣流量(PEF)恢復(fù)正常;有效:臨床癥狀明顯緩解,日間或夜間癥狀評(píng)分[7]減少2分,PEF達(dá)預(yù)計(jì)值的80%;無(wú)效:臨床癥狀無(wú)緩解或加重,日間或夜間癥狀評(píng)分減少<2分,PEF在預(yù)計(jì)值<80 %??傆行?(顯效+有效)/總例數(shù)×100%。
1.5統(tǒng)計(jì)學(xué)方法應(yīng)用SPSS13.0統(tǒng)計(jì)學(xué)軟件分析,計(jì)量資料采用t檢驗(yàn),計(jì)數(shù)資料采用χ2檢驗(yàn),以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2結(jié)果
2.1兩組治療1個(gè)月后療效的比較治療1個(gè)月后,觀(guān)察組的總有效率明顯高于對(duì)照組(P<0.01,表1)。
表1 兩組治療1個(gè)月后療效的比較(例)
注:與對(duì)照組比較,①P<0.01
2.2兩組治療前后血清PDGF、Eotaxin和IL-35表達(dá)的比較治療前兩組血清PDGF、Eotaxin和IL-35的表達(dá)水平無(wú)統(tǒng)計(jì)學(xué)差異,具有可比性;治療后兩組血清PDGF、Eotaxin的表達(dá)均下降,IL-35的表達(dá)上升;但是治療后兩組PDGF、Eotaxin和IL-35表達(dá)差異有統(tǒng)計(jì)學(xué)意義。見(jiàn)表2。
表2 兩組治療前后血清PDGF、Eotaxin和IL-35表達(dá)的比較(n=103)
注:與本組治療前比較,①P<0.05;與治療后對(duì)照組比較,②P<0.05
3討論
哮喘是由多種細(xì)胞和細(xì)胞組分參與的氣道慢性炎性疾病,免疫相關(guān)因子和炎性因子均參與病變的進(jìn)展。PDGF是哮喘病變形成和進(jìn)展中的重要蛋白,PDGF在肺組織和氣道平滑肌中的表達(dá)升高,不僅具有氣道重塑作用,還對(duì)氣道平滑肌細(xì)胞的增生有重要影響[8-9]。有研究認(rèn)為,PDGF可能作為刺激物可以直接促進(jìn)NF-κB的活性,而相關(guān)藥物的拮抗作用,可以抑制氣道壁的增厚和持續(xù)的氣道反應(yīng)性[10-11]。Eotaxin主要來(lái)源于內(nèi)皮細(xì)胞、肺泡上皮細(xì)胞和巨噬細(xì)胞,漿細(xì)胞也可以形成少量的Eotaxin[12]。Eotaxin作為一種選擇性嗜酸性粒細(xì)胞趨化因子,同時(shí)也是嗜酸性粒細(xì)胞活化的激動(dòng)劑,可以結(jié)合表面受體,引起過(guò)敏性炎癥損傷[13-14]。也有研究顯示,Eotaxin在氣道嗜酸性粒細(xì)胞浸潤(rùn)中起重要的作用,同時(shí)可以使肥大細(xì)胞向氣道方向進(jìn)行遷移,參與免疫因子的募集[15]。IL-35是白細(xì)胞介素家族的新成員,主要由Treg分泌,在正常機(jī)體中的表達(dá)穩(wěn)定,主要發(fā)揮抑制炎性反應(yīng)及免疫因子活性的負(fù)向調(diào)節(jié)作用[16-17]。有研究認(rèn)為,IL-35可以抑制炎癥反應(yīng),并防止過(guò)度的自身免疫反應(yīng)的發(fā)生[18]。動(dòng)物實(shí)驗(yàn)研究顯示,IL-35在經(jīng)樹(shù)突狀細(xì)胞刺激后產(chǎn)生,可以抑制外周血中CD4和CD8陽(yáng)性的T細(xì)胞反應(yīng),抑制過(guò)敏性病變的進(jìn)展[19-20]。
本研究結(jié)果顯示,應(yīng)用舒利迭治療兒童哮喘,療效明確,臨床中可以積極應(yīng)用。舒利迭是沙美特羅/丙酸氟替卡松復(fù)方制劑。沙美特羅在吸入后可以均勻沉積在氣道黏膜,有效刺激細(xì)胞內(nèi)的腺苷酸環(huán)化酶,松弛支氣管平滑肌,并維持在12 h以上[21]。丙酸氟替卡松的作用有:(1)高脂溶性特征,對(duì)糖皮質(zhì)激素受體有很高的親和力,患兒吸入給藥后,在肺部停留時(shí)間較長(zhǎng),對(duì)抑制炎癥反應(yīng)效果明顯;(2)通過(guò)減少β2受體的脫敏來(lái)維持β2受體的敏感性,增強(qiáng)沙美特羅對(duì)平滑肌的解痙作用。沙美特羅/丙酸氟替卡松兩種成分療效上互補(bǔ),劑量準(zhǔn)確,均勻吸入,治療過(guò)程中的依從性好,患兒易于接受和掌握[22-23]。
本研究結(jié)果還顯示,治療后兩組血清PDGF和Eotaxin的表達(dá)均下降,而IL-35的表達(dá)上升,但是治療后觀(guān)察組PDGF和Eotaxin的表達(dá)明顯低于對(duì)照組,IL-35的表達(dá)明顯高于對(duì)照組,提示舒利迭對(duì)PDGF、Eotaxin和IL-35的調(diào)控作用更強(qiáng)。即舒利迭能更有效地調(diào)節(jié)PDGF介導(dǎo)的氣道重塑作用,調(diào)節(jié)Eotaxin和IL-35介導(dǎo)的炎性反應(yīng)平衡。PDGF具有高效的氣道重塑作用,當(dāng)其表達(dá)降低后,使氣道的纖維化作用減弱,促進(jìn)損傷的平滑肌細(xì)胞再生能力增強(qiáng),氣道的結(jié)構(gòu)更趨正常,同時(shí)細(xì)胞外基質(zhì)的降解作用減弱,使氣道的收縮程度減低[24]。而Eotaxin表達(dá)下調(diào),減少了由Eotaxin誘導(dǎo)的免疫性級(jí)聯(lián)反應(yīng)的形成,使氣道的變應(yīng)性改變減弱[25],機(jī)體的致敏程度下降。IL-35治療后明顯升高,使哮喘患兒炎性反應(yīng)程度下降,也使抗炎介質(zhì)介導(dǎo)的炎性保護(hù)因子升高,炎細(xì)胞活化的作用下降,內(nèi)環(huán)境更趨優(yōu)化[26]。但舒利迭對(duì)PDGF、Eotaxin和IL-35的具體調(diào)節(jié)作用及相關(guān)通路機(jī)理尚需更多基礎(chǔ)研究來(lái)證實(shí)。
綜上所述,舒利迭治療兒童哮喘的療效明顯,可能是通過(guò)有效下調(diào)血清PDGF和Eotaxin的表達(dá),上調(diào)血清IL-35的表達(dá),優(yōu)化內(nèi)環(huán)境而實(shí)現(xiàn)的,值得在臨床積極應(yīng)用。
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Curative effect of seretide in treatment of asthma of children and its influence on serum PDGF, Eotaxin and IL-35
Yang Zhenpeng1, Li Min1, Kou Yongmei1, Wu Bingmei1, Zhao Yongsheng1, Li Shilong2, Li Dan11. Department of Pediatrics, People's Hospital of Tangshan City, Tangshan, Hebei, 063001, China; 2. Department of Laboratory, People's Hospital of Tangshan City, Tangshan, Hebei, 063001, China
[Abstract]ObjectiveTo explore the clinical curative effect of seretide in the treatment of asthma of children and observe the influence of seretide on platelet-derived growth factor (PDGF), eosinophil chemotactic factor (Eotaxin) and interleukin-35 (IL-35) in serum. Methods Total 206 children with bronchial asthma to receive treatment in our hospital were selected and randomly divided into two groups. In the control group (n=103), flixotide was used for the treatment; in the observation group (n=103), seretide was used for the treatment. Before and after the treatment, the expression levels of PDFG, Eotaxin and IL-35 in serum of the children were examined, respectively. ResultsAfter the treatment for one month, the overall effective rate of the observation group was significantly higher than that of the control group, and the expression levels of PDGF and Eotaxin in both groups decreased but that of IL-35 increased; however, after the treatment, the improvement of the foresaid three indexes in the observation group was significantly greater than that in the control group (P<0.05). Conclusion Seretide can improve the treatment effect on asthma of children, regulate effectively the content of PDGF, Eotaxin and IL-35 in serum, and optimize the balance between the humoral environment and cytokine balance, so it may be positively used for clinical application.
[Key words]children; asthma; seretide; PDGF; Eotaxin; IL-35
(收稿日期:2014-09-28)
文章編號(hào)1004-0188(2015)04-0374-04
doi:10.3969/j.issn.1004-0188.2015.04.010
中圖分類(lèi)號(hào)R 725.6
文獻(xiàn)標(biāo)識(shí)碼A