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Toll樣受體9配體CpG-ODN鼻內(nèi)應(yīng)用對(duì)變應(yīng)性聯(lián)合氣道疾病炎性反應(yīng)的影響

發(fā)布時(shí)間:2018-03-29 04:29

  本文選題:支氣管哮喘 切入點(diǎn):變應(yīng)性鼻炎 出處:《中國(guó)病理生理雜志》2016年10期


【摘要】:目的:探討免疫刺激序列Cp G寡聚脫氧核苷酸(Cp G-ODN)鼻內(nèi)應(yīng)用與皮下注射對(duì)變應(yīng)性聯(lián)合氣道疾病(ACAD)模型小鼠下氣道炎性反應(yīng)的影響。方法:30只清潔級(jí)雌性BALB/c鼠隨機(jī)分為正常對(duì)照組(control組)、變應(yīng)性鼻炎組(AR組)、變應(yīng)性聯(lián)合氣道疾病組(ACAD組)、變應(yīng)性聯(lián)合氣道疾病Cp G-ODN鼻內(nèi)滴入組(Cp G i.n.組)和變應(yīng)性聯(lián)合氣道疾病Cp G-ODN皮下注射組(Cp G i.d.組)。實(shí)驗(yàn)組動(dòng)物依次進(jìn)行腹腔卵白蛋白(OVA)和氫氧化鋁凝膠基礎(chǔ)致敏和3次鼻腔激發(fā),此后OVA或生理鹽水(NS)霧化氣道激發(fā),正常對(duì)照組則給予NS。Cp G i.n.組和Cp G i.d.組分別給予10.0μg Cp G-ODN滴鼻和皮下注射,其它組給予NS滴鼻或皮下注射。觀察Cp GODN干預(yù)后對(duì)鼻腔及下氣道病理變化及評(píng)分,并對(duì)支氣管肺泡灌洗液(BALF)行白細(xì)胞分類及嗜酸性粒細(xì)胞計(jì)數(shù),ELISA法測(cè)定BALF和脾臟中細(xì)胞因子IL-4、IL-5、IL-13和IFN-γ,以及血清OVA特異性Ig E。結(jié)果:炎癥細(xì)胞浸潤(rùn)評(píng)分示ACAD組小鼠肺部的病理改變程度高于control組和AR組(P0.01);Cp G i.n.組炎癥評(píng)分較ACAD組下降,差異有統(tǒng)計(jì)學(xué)顯著性(P0.05),而Cp G i.d.組炎癥評(píng)分較ACAD組略有下降,但差異無統(tǒng)計(jì)學(xué)意義。Cp G i.n.組BALF中的白細(xì)胞總數(shù)、EOS絕對(duì)值計(jì)數(shù)、EOS百分比、BALF和脾臟淋巴細(xì)胞上清液中Th2細(xì)胞因子較ACAD組降低,差異具有統(tǒng)計(jì)學(xué)顯著性(P0.01)。Cp G i.d.組上述指標(biāo)略低于ACAD組,但差異無統(tǒng)計(jì)學(xué)顯著性。Cp G i.n.組血清的OVA特異性Ig E較ACAD組下降,差異有統(tǒng)計(jì)學(xué)顯著性(P0.05),而Cp G i.d.組與ACAD組比較有所下降,但差異無統(tǒng)計(jì)學(xué)顯著性。結(jié)論:Cp G-ODN可通過抑制變應(yīng)性鼻炎而抑制變應(yīng)性聯(lián)合氣道疾病小鼠的下氣道炎性反應(yīng),鼻內(nèi)應(yīng)用可能較皮下注射更有效。
[Abstract]:Objective: to investigate the effect of intranasal application and subcutaneous injection of CpG oligodeoxynucleotide oligodeoxynucleotides (CpG-ODN) on the inflammatory response of inferior airway in mice with allergic combined airway disease and ACAD.Methods: 30 clean female BALB/c mice were randomly assigned. The patients were divided into normal control group, allergic rhinitis group and AR group, allergic combined airway disease group with ACAD group, allergic combined airway disease CP G-ODN intranasal drip group with CpG i.n.) and allergic combined airway disease subcutaneous injection group with CP G-ODN. The experimental group was sensitized by ovalbumin (OVA), aluminum hydroxide gel and nasal cavity three times. After that, OVA or normal saline (NS) atomized airway was stimulated, while the normal control group was given 10.0 渭 g CP G-ODN intranasal drip and subcutaneous injection, while the normal control group was given NS.Cp G i.n. and CP G i.d. group, respectively. Other groups were given NS nasal drip or subcutaneous injection. The pathological changes and scores of nasal cavity and lower airway were observed after CP GODN intervention. Leukocyte classification and eosinophilic granulocyte count Elisa were performed on bronchoalveolar lavage fluid (BALF) to detect BALF, IL-4, IL-5, IL-13 and IFN- 緯, as well as serum OVA specific Ig E.Results: inflammatory cell infiltration score showed lung of ACAD group mice. The degree of pathological changes in control group and AR group was higher than that in ACAD group, and the inflammatory score in CP G i.n. group was lower than that in ACAD group. The inflammatory score of CP G i.d. group was slightly lower than that of ACAD group. However, there was no significant difference in the absolute value of total white blood cell count in BALF and the percentage of Th2 cytokines in the supernatant of spleen lymphocytes and the percentage of Th2 in the supernatant of spleen lymphocytes in group C. CpG i.n. was lower than that in group ACAD. The difference was statistically significant (P 0.01) .CpG i.d. the above indexes were slightly lower than those in ACAD group, but there was no significant difference in OVA specific IgE between ACAD group and CpG i.d. group. The difference was statistically significant (P 0.05), while that of CP G i.d. group was lower than that of ACAD group, but the difference was not statistically significant. Conclusion the lower airway inflammatory response of mice with allergic rhinitis can be inhibited by inhibiting allergic rhinitis. Intranasal administration may be more effective than subcutaneous injection.
【作者單位】: 中山大學(xué)附屬第三醫(yī)院呼吸內(nèi)科中山大學(xué)呼吸疾病研究所;中山大學(xué)附屬第三醫(yī)院兒科;中山大學(xué)附屬第三醫(yī)院耳鼻咽喉頭頸外科;
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81470220) 廣東省自然科學(xué)基金資助項(xiàng)目(No.S2013010015990)
【分類號(hào)】:R56;R765.21

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