CAJ | 학술논문

目的：观察新型布尼亚病毒感染后病毒载量、血清细胞因子与组织损伤的关系，探讨该病毒感染水平对组织损伤及预后的影响。方法南京医科大学第一附属医院感染病科2011年5月至2012年7月门诊及住院的新型布尼亚病毒感染的严重发热伴血小板减少综合征（SFTS）患者24例，根据患者临床预后分为痊愈组21例和死亡组3例。另选取南京市中心血站健康献血者32名作为对照。采用荧光定量 PCR 检测血清病毒载量，用流式细胞仪动态定量检测患者血清中 Th1、Th2、Th17细胞因子，分析其与血清酶学、白细胞和血小板之间的关系。组间资料采用秩和检验，血清病毒载量与血清中细胞因子含量、血细胞计数、组织损伤的相关性采用 Spearman 相关分析。结果24例患者新型布尼亚病毒 RNA 检测结果均为阳性。痊愈组21例患者中有2例病毒载量＞7．0 lg 拷贝/mL。死亡组3例患者的病毒载量分别为6．7 lg 拷贝/mL、8．8 lg 拷贝/mL 和9．8 lg 拷贝/mL。SFTS 痊愈组患者在病程第5天和第7天，血清 IL-6分别为21．76和7．12 pg/mL，显著高于健康对照组的2．82 pg/mL，差异均有统计学意义（均 P ＜0．05）。SFTS 痊愈组患者病程第5天、第7天和第9天，血清 IL-10分别为14．33、14．13和3．01 pg/mL，显著高于健康对照组的1．56 pg/mL。死亡组患者在病程第7天、第9天，血清IL-6为137．61和1450．83 pg/mL，IL-10为50．26和49．43 pg/mL，较痊愈组患者增高，差异均有统计学意义（均 P ＜0．05）；病程中 SFTS 患者血清 IL-2、IL-4则显著低于健康对照组（均 P ＜0．05）。SFTS痊愈组患者白细胞和血小板计数的最低值出现在病程初期，血清 ALT、AST、乳酸脱氢酶（LDH）、CK 等均明显高于正常范围。相关性分析显示，SFTS 患者血清 IL-6、IL-10与血小板计数呈负相关（r 值分别为-0．390和-0．608，均 P ＜0．01），与病毒载量（r 值分别为0．560和0．758）、ALT（r 值分别为0．412和0．390）、AST（r 值分别为0．686和0．764）、LDH（r 值分别为0．633和0．677）、CK（r 值分别为0．527和0．636）等酶学指标呈正相关（均 P ＜0．01）。结论SFTS 患者血清病毒载量、IL-6、IL-10以及血清酶学水平与疾病严重程度密切相关，新型布尼亚病毒感染后血清中炎性因子和抑炎因子风暴，可能参与了SFTS 患者的免疫病理损伤。目的：觀察新型佈尼亞病毒感染後病毒載量、血清細胞因子與組織損傷的關繫，探討該病毒感染水平對組織損傷及預後的影響。方法南京醫科大學第一附屬醫院感染病科2011年5月至2012年7月門診及住院的新型佈尼亞病毒感染的嚴重髮熱伴血小闆減少綜閤徵（SFTS）患者24例，根據患者臨床預後分為痊愈組21例和死亡組3例。另選取南京市中心血站健康獻血者32名作為對照。採用熒光定量 PCR 檢測血清病毒載量，用流式細胞儀動態定量檢測患者血清中 Th1、Th2、Th17細胞因子，分析其與血清酶學、白細胞和血小闆之間的關繫。組間資料採用秩和檢驗，血清病毒載量與血清中細胞因子含量、血細胞計數、組織損傷的相關性採用 Spearman 相關分析。結果24例患者新型佈尼亞病毒 RNA 檢測結果均為暘性。痊愈組21例患者中有2例病毒載量＞7．0 lg 拷貝/mL。死亡組3例患者的病毒載量分彆為6．7 lg 拷貝/mL、8．8 lg 拷貝/mL 和9．8 lg 拷貝/mL。SFTS 痊愈組患者在病程第5天和第7天，血清 IL-6分彆為21．76和7．12 pg/mL，顯著高于健康對照組的2．82 pg/mL，差異均有統計學意義（均 P ＜0．05）。SFTS 痊愈組患者病程第5天、第7天和第9天，血清 IL-10分彆為14．33、14．13和3．01 pg/mL，顯著高于健康對照組的1．56 pg/mL。死亡組患者在病程第7天、第9天，血清IL-6為137．61和1450．83 pg/mL，IL-10為50．26和49．43 pg/mL，較痊愈組患者增高，差異均有統計學意義（均 P ＜0．05）；病程中 SFTS 患者血清 IL-2、IL-4則顯著低于健康對照組（均 P ＜0．05）。SFTS痊愈組患者白細胞和血小闆計數的最低值齣現在病程初期，血清 ALT、AST、乳痠脫氫酶（LDH）、CK 等均明顯高于正常範圍。相關性分析顯示，SFTS 患者血清 IL-6、IL-10與血小闆計數呈負相關（r 值分彆為-0．390和-0．608，均 P ＜0．01），與病毒載量（r 值分彆為0．560和0．758）、ALT（r 值分彆為0．412和0．390）、AST（r 值分彆為0．686和0．764）、LDH（r 值分彆為0．633和0．677）、CK（r 值分彆為0．527和0．636）等酶學指標呈正相關（均 P ＜0．01）。結論SFTS 患者血清病毒載量、IL-6、IL-10以及血清酶學水平與疾病嚴重程度密切相關，新型佈尼亞病毒感染後血清中炎性因子和抑炎因子風暴，可能參與瞭SFTS 患者的免疫病理損傷。
목적：관찰신형포니아병독감염후병독재량、혈청세포인자여조직손상적관계，탐토해병독감염수평대조직손상급예후적영향。방법남경의과대학제일부속의원감염병과2011년5월지2012년7월문진급주원적신형포니아병독감염적엄중발열반혈소판감소종합정（SFTS）환자24례，근거환자림상예후분위전유조21례화사망조3례。령선취남경시중심혈참건강헌혈자32명작위대조。채용형광정량 PCR 검측혈청병독재량，용류식세포의동태정량검측환자혈청중 Th1、Th2、Th17세포인자，분석기여혈청매학、백세포화혈소판지간적관계。조간자료채용질화검험，혈청병독재량여혈청중세포인자함량、혈세포계수、조직손상적상관성채용 Spearman 상관분석。결과24례환자신형포니아병독 RNA 검측결과균위양성。전유조21례환자중유2례병독재량＞7．0 lg 고패/mL。사망조3례환자적병독재량분별위6．7 lg 고패/mL、8．8 lg 고패/mL 화9．8 lg 고패/mL。SFTS 전유조환자재병정제5천화제7천，혈청 IL-6분별위21．76화7．12 pg/mL，현저고우건강대조조적2．82 pg/mL，차이균유통계학의의（균 P ＜0．05）。SFTS 전유조환자병정제5천、제7천화제9천，혈청 IL-10분별위14．33、14．13화3．01 pg/mL，현저고우건강대조조적1．56 pg/mL。사망조환자재병정제7천、제9천，혈청IL-6위137．61화1450．83 pg/mL，IL-10위50．26화49．43 pg/mL，교전유조환자증고，차이균유통계학의의（균 P ＜0．05）；병정중 SFTS 환자혈청 IL-2、IL-4칙현저저우건강대조조（균 P ＜0．05）。SFTS전유조환자백세포화혈소판계수적최저치출현재병정초기，혈청 ALT、AST、유산탈경매（LDH）、CK 등균명현고우정상범위。상관성분석현시，SFTS 환자혈청 IL-6、IL-10여혈소판계수정부상관（r 치분별위-0．390화-0．608，균 P ＜0．01），여병독재량（r 치분별위0．560화0．758）、ALT（r 치분별위0．412화0．390）、AST（r 치분별위0．686화0．764）、LDH（r 치분별위0．633화0．677）、CK（r 치분별위0．527화0．636）등매학지표정정상관（균 P ＜0．01）。결론SFTS 환자혈청병독재량、IL-6、IL-10이급혈청매학수평여질병엄중정도밀절상관，신형포니아병독감염후혈청중염성인자화억염인자풍폭，가능삼여료SFTS 환자적면역병리손상。
Objective To observe the relationship of viral load,serum cytokines and tissue damage after severe fever with thrombocytopenia syndrome virus (SFTSV)infection,and to explore the impact of SFTSV levels on tissue injury and prognosis.Methods Twenty-four ambulatory and hospitalized patients who were infected with SFTSV were enrolled between May 2011 and July 2012 at Department of Infectious Disease, First Affiliated Hospital with Nanjiang Medical University. According to their prognosis,they were divided into cure and death group,while 32 healthy blood donators were also enrolled from center blood station in Nanjing as control.The serum SFTSV load was detected using fluorescence quantitative polymerase chain reaction (PCR).The serum T helper (Th)1/Th2/Th17 cytokines in patients with severe fever with thrombocytopenia syndrome (SFTS)were determined dynamically and quantitatively by flow cytometry.The relationships between viral load,cytokines and serum enzymes, white blood cell (WBC),platelet (PLT)counts were analyzed.Comparisons among groups were achieved by rank sum test and correlation analysis among serum cytokines,blood cell counts and tissue damage was done by Spearman correlation test.Results All of the 24 patients showed a positive reaction to SFTSV RNA.The SFTSV loads of 21 cured cases,those of 2 were > 7.0 lg copy/mL,and those of 3 death patients were 6.7 lg copy/mL,8.8 lg copy/mL and 9.8 lg copy/mL,respectively.Serum level of interleukin (IL)-6 (21 .76 pg/mL in day 5 and 7.12 pg/mL in day 7)and IL-10 (14.33 pg/mL in day 5 , 14.13 pg/mL in day 7 and 3.01 pg/mL in day 9)of cured patients were significantly higher than those of healthy controls (IL-6:2.82 pg/mL and IL-10:1 .56 pg/mL)(P <0.05 ).At day 7 and day 9,serum levels of IL-6 of death cases were 137.61 pg/mL and 1 450.83 pg/mL,respectively and serum levels of IL-10 were 50.26 pg/mL and 49.43 pg/mL,respectively.Both of the indicators in the death group were significantly higher than those of cure group (P <0.05 ).However,serum levels of IL-2 and IL-4 were significantly lower than those in healthy control group (P <0.05 ).In the cure group,WBC and PLT counts were lowest during the early course of the disease,and serum alamine aminotransferase (ALT), aspartate aminotransferase (AST ), lactic dehydrogenase (LDH ) and creatine kinase (CK ) were significantly higher than their upper limits of normal.The correlation analysis showed that serum IL-6, IL-10 levels were negatively correlated with PLT count (r=-0.390 and -0.608,respectively;both P <0.01),and positively correlated with SFTSV load (r=0.560 and 0.758,respectively),ALT (r=0.412 and 0.390,respectively),AST (r = 0.686 and 0.764,respectively),LDH (r = 0.633 and 0.677, respectively)and CK (r =0.527 and 0.636,respectively)(all P <0.01 ).Conclusions SFTSV load, IL-6,IL-10 and serum enzyme levels are closely related to the severity of the disease.The inflammatory and anti-inflammatory cytokine storm after SFTSV infection may be involved in the immune pathological injury in patients with SFTS.