曹若瑾，王潔妤，李 耘，馬麗娜，馮 明，錢玉英

(首都醫(yī)科大學(xué)宣武醫(yī)院綜合科,北京 100053;*通訊作者,E-mail:caoruojin26@163.com)

內(nèi)源性一氧化碳在老年肺炎患者中的變化及臨床意義

曹若瑾*，王潔妤，李 耘，馬麗娜，馮 明，錢玉英

(首都醫(yī)科大學(xué)宣武醫(yī)院綜合科,北京 100053;*通訊作者,E-mail:caoruojin26@163.com)

目的 探討內(nèi)源性一氧化碳(CO)在老年人肺炎中的變化及意義。 方法 選取30例老年肺炎患者及12例中年肺炎患者,分別于急性期和恢復(fù)期抽取靜脈血測定血漿CO、TNF-α、IL-6濃度,入院時進行APACHEⅡ評分判斷患者病情嚴重程度。分別比較老年肺炎組急性期與恢復(fù)期各指標之間的差異以及相同病程的老年肺炎組和中年肺炎組間各指標之間的差異。分析老年肺炎組血漿CO與TNF-α、IL-6及APACHEⅡ評分之間的相關(guān)性。 結(jié)果 ①老年肺炎組急性期的CO、TNF-α和IL-6水平較中年組明顯升高(P<0.01)。②老年肺炎患者的血清CO、TNF-α、IL-6水平急性期明顯高于恢復(fù)期(P<0.01),多元相關(guān)分析顯示CO與TNF-α、IL-6水平及APACHEⅡ評分均呈顯著正相關(guān)(P<0.01)。 結(jié)論 老年肺炎患者內(nèi)源性CO水平明顯升高,且與炎癥反應(yīng)、病情輕重程度有關(guān);內(nèi)源性CO對老年肺炎患者病情和預(yù)后判斷具有一定的臨床意義。

老年人; 肺炎; 一氧化碳; 腫瘤壞死因子-α; 白介素-6

老年人肺炎發(fā)病率高,且病情相對嚴重。近年來研究表明血紅素氧合酶-1(HO-1)的誘導(dǎo)對保護肺部,抵抗氧化物所致肺損傷起關(guān)鍵性作用,并推論其作用機制與其降解血紅素的分解產(chǎn)物一氧化碳(CO)密切相關(guān)[1-3]。本文研究了內(nèi)源性CO在老年人肺炎中的變化及意義,CO與病情輕重的關(guān)系,并與中年組進行比較,探討老年人肺部感染性疾病的防御性反應(yīng)。

1 對象與方法

1.1 研究對象

老年(年齡>60歲)肺炎患者30例,其中男性25例,女性5例,年齡65-90歲,平均年齡(75±7)歲。中年(年齡>35歲)肺炎患者12例,其中男性11例,女性1例,年齡36-56歲,平均年齡(48±6)歲。均滿足以下入組標準:①發(fā)熱,體溫>38 ℃,未曾治療或治療后仍發(fā)熱;②胸部影像學(xué)提示為肺炎;③未使用激素,血脂無異常(此兩項可影響CO數(shù)值)。

1.2 研究方法

1.2.1 檢測指標 分別于入院時(急性期)及經(jīng)治療后體溫正常5-10 d(恢復(fù)期)晨起空腹抽取靜脈血,測血漿CO、腫瘤壞死因子(TNF)-α和白介素(IL)-6的濃度;檢測血常規(guī)、腎功能、血鉀鈉,抽取動脈血即刻送檢血氣分析,行胸片或胸部CT,根據(jù)血清TNF-α、IL-6水平判斷炎癥反應(yīng)水平,根據(jù)APACHEⅡ評分判斷患者病情輕重程度。

1.2.2 檢測方法 CO測定應(yīng)用一氧化碳血紅蛋白雙波長測定法,TNF-α及IL-6測定應(yīng)用雙抗體夾心ELISA法。

1.3 統(tǒng)計學(xué)處理

應(yīng)用SPSS11.5統(tǒng)計軟件進行統(tǒng)計分析,因IL-6濃度呈非正態(tài)分布,故取對數(shù)LG10轉(zhuǎn)換為正態(tài)分布,以便進行統(tǒng)計分析。老年組的急性期及恢復(fù)期間各指標比較采用配對t檢驗,老年肺炎組和中年肺炎組間各指標比較采用兩樣本t檢驗。CO與TNF-α、IL-6和APACHEⅡ評分之間的相關(guān)性分析采用Pearson相關(guān)。

2 結(jié)果

2.1 老年肺炎組與中年肺炎組各指標間比較

老年肺炎組急性期的CO、TNF-α和IL-6水平均高于中年肺炎組,差異均有統(tǒng)計學(xué)意義(P<0.01,見表1)?；謴?fù)期的CO、TNF-α和IL-6水平亦均高于中年肺炎組,但差異無統(tǒng)計學(xué)意義(P>0.05,見表1)。老年肺炎組急性期的APACHEⅡ評分為(8.5±2.2)分;中年肺炎組APACHEⅡ評分為(4.3±2.3)分。

2.2 老年肺炎組在急性期和恢復(fù)期不同病程中各指標的變化

2.2.1 老年肺炎患者急性期和恢復(fù)期血清CO、TNF-α、IL-6水平的比較 老年肺炎組急性期的CO、TNF-α、IL-6水平均明顯高于恢復(fù)期,差異有統(tǒng)計學(xué)意義(P<0.01,見表1)。

表1 老年肺炎組與中年肺炎組不同病程各指標的比較

Table 1 Comparison of CO, TNF-α and IL-6 in plasma among different groups

病程分組CO (mg/L) TNF-α (pg/ml) IL-6 (pg/ml) 急性期老年組0.60±0.08**##284.73±38.07**##1.16±0.16**##中年組0.45±0.08203.23±33.290.93±0.15恢復(fù)期老年組0.28±0.06148.90±36.580.31±0.12中年組0.20±0.09132.40±50.300.25±0.16

與相同病程的中年肺炎組相比較**P<0.01;與老年肺炎恢復(fù)期相比較,##P<0.01

2.2.2 老年肺炎患者急性期血清CO與TNF-α、IL-6水平、APACHEⅡ評分的多元相關(guān)分析 將老年肺炎患者急性期的血清CO水平與TNF-α、IL-6水平、APACHEⅡ評分進行多元相關(guān)分析,結(jié)果顯示,CO與IL-6、TNF-α與APACHEⅡ評分均呈正相關(guān),Pearson相關(guān)系數(shù)分別為0.932,0.902和0.513,差異有統(tǒng)計學(xué)意義(P<0.001,見表2)。

表2 老年肺炎患者急性期CO與TNF-α、IL-6以及APACHEⅡ評分的相關(guān)性

Table 2 The correlation between CO and TNF-α,IL-6 in plasma and APACHEⅡ score in old patients with pneumonia at the acute stage

指標rPIL-60.932<0.001TNF-α0.902<0.001APACHEⅡ評分0.513<0.001

3 討論

老年肺炎組急性期的血漿CO、TNF-α、IL-6水平較恢復(fù)期明顯升高。感染性因素及有害刺激經(jīng)氣道入肺,刺激肺泡的巨噬細胞產(chǎn)生TNF-α、IL-6、IL-8和少量IL-1,它們及其他中性細胞趨化因子吸引中性粒細胞,啟動炎癥反應(yīng)。IL-6在體內(nèi)激發(fā)和協(xié)調(diào)炎癥反應(yīng)中起到主要作用。臨床研究證明很多感染性、炎癥性惡性病變時IL-6水平增高[4,5]。TNF-α能促使巨噬細胞和中性粒細胞趨化及黏附,提示TNF-α在正常炎癥的起始階段起著重要作用。目前已明確HO-1降解血紅素生成CO是內(nèi)源性CO產(chǎn)生的主要途徑,故可判斷肺部炎癥性疾病時CO升高是由于某些因素誘導(dǎo)HO-1基因表達、HO-1蛋白質(zhì)合成和活性增加所致。其可能機制為:①炎癥刺激產(chǎn)生的TNF-α和IL-6進入體循環(huán),可通過下丘腦誘導(dǎo)發(fā)熱,并促使肝細胞產(chǎn)生HO-1,從而CO生成增加。②目前已鑒定出肺血管平滑肌細胞、內(nèi)皮細胞、Ⅱ型肺上皮細胞、氣道上皮細胞和肺泡巨噬細胞等存在HO-1。肺部急性炎癥造成的低氧,以及內(nèi)毒素和細胞因子等可誘導(dǎo)其活性成倍地增加,CO產(chǎn)生增多,繼而發(fā)揮生理或病理作用[6]。③感染時體內(nèi)誘導(dǎo)型一氧化氮合成酶(iNOS)、可溶性鳥苷酸環(huán)化酶(sGC)等作為HO-1的自然底物誘導(dǎo)HO-1蛋白表達和活性增加。內(nèi)源性NO增加能誘導(dǎo)HO-1 mRNA的轉(zhuǎn)錄。④肺炎患者存在氧化應(yīng)激,使體內(nèi)氧自由基增多,氧自由基通過激活HO-1基因啟動區(qū)NF-κB和AP-1,調(diào)節(jié)HO-1 mRNA轉(zhuǎn)錄和蛋白質(zhì)合成增加[7]。因此,炎癥急性期IL-6、TNF-α、CO均明顯升高，并隨炎癥控制于恢復(fù)期逐漸降低。

本實驗結(jié)果還顯示,老年肺炎組的CO與TNF-α、IL-6及APACHEⅡ評分均呈顯著正相關(guān),說明內(nèi)源性CO與炎癥反應(yīng)程度、病情輕重程度有關(guān),即炎癥反應(yīng)重、病情重的患者CO升高更明顯。從臨床角度證實內(nèi)源性CO在危重病癥的病理過程中發(fā)揮作用。因此,檢測血漿CO含量,并結(jié)合病人的臨床表現(xiàn),可能成為監(jiān)測患者病情嚴重程度和了解預(yù)后的新指標。據(jù)報道,CO具有清除自由基、下調(diào)炎性介質(zhì)、增加抗炎細胞因子、抑制白細胞活化及與內(nèi)皮細胞黏附、減少炎癥細胞浸潤、具有抗氧化、抗炎癥和抑制細胞凋亡等作用[8,9]。因此可以通過HO-1誘導(dǎo)劑來調(diào)控HO-1的表達,提高機體CO水平,增加機體抗氧化、抗炎等作用[10,11],減輕肺水腫及肺毛細血管通透性[12]。Fredenburgh等[1]證實在狒狒的肺炎鏈球菌肺炎的模型中通過吸入CO使CO-Hb水平升高,可以有效減輕肺損傷。臨床上也已經(jīng)有應(yīng)用CO吸入療法治療肺部感染性疾病的臨床研究在開展[13]。這對于臨床重癥肺炎也許可以提供一條新的治療途徑。

目前對于老年人肺部炎癥性疾病時HO-1/CO系統(tǒng)的誘導(dǎo)是否與中青年人不同知之甚少。本研究結(jié)果顯示老年肺炎組的CO水平于急性期比中年肺炎組高,且差異具有統(tǒng)計學(xué)意義。但是老年肺炎組急性期的APACHEⅡ評分為(8.5±2.2)分;中年肺炎組APACHEⅡ評分為(4.3±2.3)分,說明老年肺炎組的病情較中年組更重。TNF-α、IL-6等炎性因子也顯著增高,且各因素相關(guān)分析顯示內(nèi)源性CO與炎癥反應(yīng)、病情輕重程度呈正相關(guān)。我們分析認為以上結(jié)果主要由于老年組與中年組病情輕重不同造成的差異,老年肺炎組的CO水平升高尚不能說明老年人肺部炎癥性疾病時HO-1/CO的誘導(dǎo)強于中年人。需進一步觀察病情程度一致的老年人與中年人的HO-1/CO的誘導(dǎo)才能說明問題。

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Role of endogenous carbon monoxide in old patients with pneumonia

CAO Ruojin*,WANG Jieyu,LI Yun,MA Lina,FENG Ming,QIAN Yuying

(GeneralDepartment,XuanwuHospital,CapitalMedicalUniversity,Beijing100053,China;*Correspondingauthor,E-mail:caoruojin26@163.com)

ObjectiveTo investigate the changes and significance of endogenous carbon monoxide(CO)in old patients with pneumonia.MethodsThirty old patients and twelve adult patients with pneumonia were collected. Blood samples of the selected patients were respectively collected at the acute stage and convalescent stage. The levels of CO, tumor necrosis factor(TNF)-α and interleukin(IL)-6 in plasma were examined. According to APACHEⅡscores, the severity of the patients were estimated. The indexes were compared between the old patients with pneumonia at the acute stage and the convalescent stage, and between the old patients and the adult patients with pneumonia at the same stage. The correlation between plasma CO and TNF-α,IL-6,APACHEⅡ scores were analyzed respectively in the old patients with pneumonia.Results①The CO level in the old patients at the acute stage was significantly higher than that of the adult patients(P<0.01).②The levels of CO,TNF-α and IL-6 were higher in old patients with pneumonia at the acute stage than that at the convalescent stage(P<0.01).The level of CO was positively correlated with APACHEⅡ scores,TNF-α and IL-6, respectively (P<0.01).Conclusion①Endogenous CO increases in old patients with pneumonia. ②The level of plasma CO may serve as a marker of severity and prognosis of pneumonia in old patients.

aged; pneumonia; carbon monoxide; tumor necrosis factor-α; interleukin-6

曹若瑾,女,1974-01生,碩士,副主任醫(yī)師,E-mail:caoruojin26@163.com

2017-04-12

R563.1

A

1007-6611(2017)08-0827-03

10.13753/j.issn.1007-6611.2017.08.015