重型乙型腦炎患者腎上腺皮質(zhì)激素的作用

林建英

【摘要】 目的 探討地塞米松對(duì)乙型腦炎患兒的病情、預(yù)后及腦脊液α-腫瘤壞死因子(TNF-α)與干擾素(IFN)的影響。方法 把33例重型極期乙腦患兒隨機(jī)分為兩組,地塞米松組18例給予靜脈地塞米松針4~5 d; 對(duì)照組15例則不用地塞米松。觀察比較兩組的臨床過程和腦脊液TNF-α與IFN的變化。結(jié)果 入院時(shí)兩組的主要臨床特點(diǎn)和腦脊液TNF-α與IFN的水平相似, 4~5 d后地塞米松組的臨床癥狀改善情況優(yōu)于對(duì)照組,但兩組的腦脊液TNF-α與IFN的水平卻無明顯改變,并經(jīng)過一個(gè)月的觀察地塞米松組的恢復(fù)期癥狀發(fā)生率也低于對(duì)照組。結(jié)論 對(duì)重型極期乙腦患兒給予靜脈地塞米松可以改善病情,減輕癥狀,減少恢復(fù)期癥狀的發(fā)生。

【關(guān)鍵詞】 乙腦;地塞米松;病情

Effect of adrenal cortical hormone on the severe type of patients with epidemic encephalitis B in children

LIN Jian-ying.The First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100, China

【Abstract】 Objective To investigate the influence of adrenal cortical hormone on the patient's condition, prognosis and the levels of TNF-α and TNF-γ in cerebrospinal fluid in children with epidemic encephalitis B.Methods 33 cases of severe type of patients with epidemic encephalitis B were divided into two groups randomly, i e dexamethasone-treated group (18) and the control group(15) . In the treated group, patients were treated with intravenous injection of dexamethasone at a dosage of 8 mg/kg/day for 0.4~0.8 or 5 days; while in the control, no dexammethasone was given. The clinical courses and the changes on levels of TNF-α and IFN-γ in cerebrospinal fluid were compared between these two groups of patients.Results It was demonstrated that the clinical courses and the levels of cytokines in cerebrospinal fluid at time of admission appeared to be similar, however, the improvement of clinical course in the-treated group was better than those of the control group. As to the levels of cytokines in cerebrospinal fluid, there were no significant difference between these two groups. In addition, after one month observation, the rate of symptom development in the convalescence of the treated group was lower than that of the control group.Conclusion From the above observations, it is evident that treatment with intravenous injection of dexamethasone in severe cases with epidemic encephalitis B can improve the clinical course, lessen the clinical symptoms and reduce the rate of development of symptoms in convalescence.

【Key words】 Epidemic encephalris B; Dexamethasone; Patient's condition

流行性乙型腦炎(epidemic encephalitis B,簡稱乙腦)由乙型腦炎病毒引起的以腦實(shí)質(zhì)炎癥為主要病變的人獸共患的急性傳染病;重型患兒病死率仍在10%左右,并且多數(shù)發(fā)生在極期。由于乙腦沒有特效的治療方法,主要是積極對(duì)癥治療和護(hù)理。目前激素在乙腦中的作用仍有不同看法,Hoke等［1］報(bào)道使用大劑量激素沒有滿意療效;而何時(shí)軍等［2］報(bào)道大劑量激素能抑制顱內(nèi)炎癥反應(yīng)水平,阻止病情惡化。因此激素的應(yīng)用及其作用機(jī)制有待進(jìn)一步探討。

1 資料與方法

1.1 一般資料 33例重型乙腦患兒均來自2007年11~12月新鄉(xiāng)醫(yī)學(xué)院第一附屬醫(yī)院感染科住院病例?；純貉逡夷X特異性IgM抗體均陽性,符合乙腦診斷及分型標(biāo)準(zhǔn)［3］。將33例隨機(jī)分為地塞米松組18例,男10例,女8例;對(duì)照組15例,男9例,女6例;年齡2~11歲。

1.2 方法 兩組年齡、最高體溫、GCS評(píng)分及腦脊液TNF-α與IFN水平均具可比性,見表1。地塞米松組給予靜脈地塞米松針0.4～0.8 mg/(kg?d),2次/d，4~5 d;對(duì)照組則不用地塞米松;其余治療相同。停用地塞米松后比較兩組最高體溫、GCS評(píng)分及腦脊液TNF-α與IFN水平;極期后經(jīng)過1個(gè)月觀察比較恢復(fù)期癥狀的發(fā)生率。TNF-α與IFN檢測采用ELISA法,試劑盒購自深圳晶美生物工程有限公司,按說明書操作。

1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 14.0軟件包進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料用t檢驗(yàn),計(jì)數(shù)資料用χ²檢驗(yàn)。

2 結(jié)果

經(jīng)治后,地塞米松組的最高體溫明顯低于對(duì)照組,GCS評(píng)分則明顯高于對(duì)照組,均有統(tǒng)計(jì)學(xué)意義,地塞米松組恢復(fù)期癥狀發(fā)生率要低于對(duì)照組,但無統(tǒng)計(jì)學(xué)意義,兩組的腦脊液TNF-α與IFN的水平卻無明顯改變,無統(tǒng)計(jì)學(xué)意義,見表2、3。

3 討論

乙腦的病情、預(yù)后同腦實(shí)質(zhì)的損害程度直接相關(guān),目前認(rèn)為通過免疫病理反應(yīng)引起腦實(shí)質(zhì)的損害是本病重要的發(fā)病機(jī)制之一,而細(xì)胞因子與宿主的免疫反應(yīng)密切相關(guān),因此調(diào)節(jié)乙腦患兒的免疫狀態(tài),提高機(jī)體的免疫保護(hù)作用而又盡量抑制免疫病理損傷是有效的治療途徑之一。TNF-α是由激活的單核巨噬細(xì)胞產(chǎn)生和分泌,其次星型膠質(zhì)細(xì)胞、小膠質(zhì)細(xì)胞及激活的T細(xì)胞也可產(chǎn)生。它是一種具有多種生物學(xué)活性的細(xì)胞因子,能直接損傷血管內(nèi)皮細(xì)胞,增加血管通透性,并誘導(dǎo)內(nèi)皮細(xì)胞表達(dá)粘附分子,刺激星型細(xì)胞分泌白細(xì)胞介素,因而可以加重炎癥反應(yīng)和腦實(shí)質(zhì)的損害。許多報(bào)道在中樞神經(jīng)系統(tǒng)感染疾病中均可見TNF-α和TNF非特異性的明顯增高［4-6］。乙腦病毒可以激發(fā)單核細(xì)胞及星型細(xì)胞產(chǎn)生大量TNF［3］,提示TNF-α參與了乙腦的免疫病理過程。IFN是由病毒或其他IFN誘生劑刺激機(jī)體產(chǎn)生的一種特殊糖蛋白,它不僅通過作用于細(xì)胞產(chǎn)生抗病毒蛋白酶而進(jìn)入抗病毒狀態(tài),還有各種生物活性,如抑制細(xì)胞增殖、抗體產(chǎn)生及遲發(fā)性變態(tài)反應(yīng),提高細(xì)胞抗原提呈能力,活化多種免疫細(xì)胞,在急性病毒感染初期起著重要作用。本結(jié)果也顯示重型乙腦患兒的腦脊液中TNF-α與IFN水平也明顯增高,同時(shí)也說明了乙腦患兒顱內(nèi)局部的免疫病理反應(yīng)在乙腦的發(fā)病過程中起了重要的作用。

腎上腺皮質(zhì)激素具有抗炎、抗毒素、抗過敏和免疫抑制等作用。不少文獻(xiàn)報(bào)道了應(yīng)用腎上腺皮質(zhì)激素治療細(xì)菌性腦膜炎,它可減少死亡率和各種神經(jīng)系統(tǒng)后遺癥的發(fā)生［7-9］。但Van等［10］報(bào)道在發(fā)展中國家的兒童急性細(xì)菌性腦膜炎中使用激素卻沒有獲得有益的效果;Simmons等［11］報(bào)道了地塞米松在治療結(jié)核性腦膜炎中所起的作用與抑制外周和局部的免疫反應(yīng)無關(guān)。本結(jié)果顯示腎上腺皮質(zhì)激素能有效控制病情,并可減少部分恢復(fù)期癥狀的發(fā)生,病程中也沒有發(fā)現(xiàn)明顯的激素副作用;同時(shí)筆者也發(fā)現(xiàn)激素治療后兩組的腦脊液TNF-α與IFN水平也相似,故推測其作用與抑制顱內(nèi)局部的免疫反應(yīng)關(guān)系不大,其他的機(jī)制可能更重要:①退熱作用:糖皮質(zhì)激素能降低體溫調(diào)節(jié)中樞對(duì)內(nèi)源性和外源性致熱原的敏感性而使體溫下降;②改善微循環(huán),增強(qiáng)機(jī)體對(duì)缺氧的耐受力等;③通過降低毛細(xì)血管的通透性,改善血腦屏障并維持其完整性,減少腦脊液的產(chǎn)生,增加腎臟的血流量和腎小球?yàn)V過率等降低顱內(nèi)壓。激素在乙腦中所起的作用有待進(jìn)一步探討。

參 考 文 獻(xiàn)

［1］ Hoke CH, Vaughn DW, Nisalak A, et al. Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. J Infect Dis, 1992, 165(4):631-637.

［2］ 何時(shí)軍, 鄭曉群, 單小鷗, 等. 大劑量地塞米松治療重型流行性乙型腦炎對(duì)腦脊液腫瘤壞死因子-α白細(xì)胞介素-6、8的影響.實(shí)用兒科臨床雜志, 2006, 21(12):781-782.

［3］ 陳灝珠. 實(shí)用內(nèi)科學(xué).人民衛(wèi)生出版社,2006:348-351.

［4］ 金玉, 薛君莉, 余唯琪, 等. 腦脊液細(xì)胞因子檢測在小兒神經(jīng)系統(tǒng)感染鑒別診斷中的意義.中華兒科雜志, 2002, 40 (4):199-201.

［5］ Babu GN, Kalita J, Misra UK. Inflammatory markers in the patients of Japanese encephalitis. Neurol Res, 2006,28(2):190-192.

［6］ Winter PM, Dung NM, Loan HT, et al. Proinflammatory cytokines and chemokines in humans with Japanese encephalitis. JInfect Dis, 2004,190(9):1618-1626.

［7］ Sinner SW, Tunkel AR. Antimicrobial agents in the treatment ofbacterial meningitis. Infect Dis Clin North Am, 2004 ,18(3):581-602.

［8］ Chaudhuri A. Adjunctive dexamethasone treatment in acute bacterial meningitis. Lancet Neurol, 2004 , 3(1):54-62.

［9］ Ahsan T, Shahid M, Mahmood T, et al.Role of dexamethasonein acute bacterial meningitis in adults. J Pak Med Assoc, 2002,52(6):233-239.

［10］ van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev, 2007 , 24 (1):4405.

［11］ Simmons CP, Thwaites GE, Quyen NT, et al. The clinical benefit of adjunctive dexamethasone in tuberculous meningitis is not associated with measurable attenuation of peripheral or local immune responses. J Immunol,2005,175(1):579-590.