CAJ | 학술논문

目的观察噬菌体对鲍曼不动杆菌引起的小鼠肠源性脓毒症的治疗效果.方法采用双层琼脂法从环境中分离鲍曼不动杆菌噬菌体.通过腹腔注射氨苄青霉素和环磷酰胺的方法,同时经口感染耐氨苄青霉素鲍曼不动杆菌,建立小鼠肠源性脓毒症模型.在细菌感染前1d、感染结束后2d,以及感染结束后6d给予噬菌体治疗,观察小鼠的存活情况.另取未给予噬菌体治疗小鼠作为对照.各组分别设6只小鼠.采用成组设计的两样本均数t检验比较噬菌体治疗组和对照组小鼠外周血和肝脏内炎症因子水平,以及肝脏和脾脏内的细菌数量.结果鲍曼不动杆菌引起肠源性脓毒症小鼠全部死亡的最小致死量为1×107 CFU/mL.在感染前、结束后2d和6 d给予噬菌体治疗,分别有2,4,3只小鼠存活,对照组全部死亡.噬菌体治疗组小鼠外周血白细胞介素(IL)-1β、肿瘤坏子因子(TNF)-α和IL-6水平分别为(105±6) ng/L,(105±11)ng/L和(104±12) ng/L,明显低于对照组(t=5.04,9.05和9.33,P＜0.01);噬菌体治疗组小鼠肝脏内的IL-1 β和TNF-α水平分别为(104 ±9) ng/L和(104±11)ng/L,亦低于对照组(t=13.70和12.80,P＜0.01),但IL-6水平治疗组与对照组比较差异无统计学意义(t=1.06,P＞0.05);噬菌体治疗组小鼠肝脏和脾脏内细菌数量分别为(2.9±1.3)×103CFU/g和(8.3±7.6)×102 CFU/g,明显低于对照组(=9.16和8.96,P＜0.01).结论噬菌体治疗鲍曼不动杆菌引起的肠源性脓毒症确切有效.
목적 관찰서균체대포만불동간균인기적소서장원성농독증적치료효과.방법 채용쌍층경지법종배경중분리포만불동간균서균체.통과복강주사안변청매소화배린선알적방법,동시경구감염내안변청매소포만불동간균,건립소서장원성농독증모형.재세균감염전1d、감염결속후2d,이급감염결속후6d급여서균체치료,관찰소서적존활정황.령취미급여서균체치료소서작위대조.각조분별설6지소서.채용성조설계적량양본균수t검험비교서균체치료조화대조조소서외주혈화간장내염증인자수평,이급간장화비장내적세균수량.결과 포만불동간균인기장원성농독증소서전부사망적최소치사량위1×107 CFU/mL.재감염전、결속후2d화6 d급여서균체치료,분별유2,4,3지소서존활,대조조전부사망.서균체치료조소서외주혈백세포개소(IL)-1β、종류배자인자(TNF)-α화IL-6수평분별위(105±6) ng/L,(105±11)ng/L화(104±12) ng/L,명현저우대조조(t=5.04,9.05화9.33,P＜0.01);서균체치료조소서간장내적IL-1 β화TNF-α수평분별위(104 ±9) ng/L화(104±11)ng/L,역저우대조조(t=13.70화12.80,P＜0.01),단IL-6수평치료조여대조조비교차이무통계학의의(t=1.06,P＞0.05);서균체치료조소서간장화비장내세균수량분별위(2.9±1.3)×103CFU/g화(8.3±7.6)×102 CFU/g,명현저우대조조(=9.16화8.96,P＜0.01).결론 서균체치료포만불동간균인기적장원성농독증학절유효.
Objective To evaluate bacteriophage therapy for gut-derived sepsis caused by Acinetobacter baumannii in mice.Methods Lyric phages of Acinetobacter baumannii were isolated from environment by using double-layer agar method.A murine model of gut-derived sepsis was established by oral administration of ampicillin-resistant Acinetobacter baumannii and injection of ampicillin and cyclophosphamide into peritoneal cavities of mice.Bacteriophage therapy were given 1 d before infection (group 1),2 d(group 2) and 6 d(group 3) after infection.The survival of the mice was observed,mice without bacteriophage therapy were as control.Independent-sample t test was performed to compare inflammatory cytokines levels in peripheral blood and liver,number of bacteria in liver and spleen between mice with and without bacteriophage therapy.Results The minimal lethal dose of Acinetobacter baumannii for mice with gut-derived sepsis was 1 × 107 CFU/mL.The survival of the mice in group 2 (4/6 survived),which were treated with bacteriophage 2 d after inoculation of Acinetobacter baumannii,was higher than those of group 1 (2/6 survived),group 3 (3/6 survived) and the control group (phage-untreated,0/6 survived).Interleukin (IL)-1 β,tumor necrosis factor (TNF)-α and IL-6 in peripheral blood in mice with bacteriophage therapy were (105 ±6) ng/L,(105 ± 11) ng/L and (104 ± 12)ng/L,which were lower than those in control group (t =5.04,9.05 and 9.33,P ＜ 0.01) ; IL-1 β and TNF-α in liver of mice with bacteriophage therapy were (104 ± 9) ng/L and (104 ± 11) ng/L,which were lower than those in the controls (t =13.70 and 12.80,P ＜0.01),but IL-6 levels were not of statistical difference between therapy and control groups (t =1.06,P ＞ 0.05).Number of bacteria in liver and spleen in mice with bacteriophage therapy were (2.9 ± 1.3) × 103CFU/g and (8.3 ±7.6) × 102 CFU/g,which were also lower than those in control group (t =9.16 and 8.96,P ＜ 0.01).Conclusions Bacteriophage therapy can be effective against gut-derived sepsis caused by Acinetobacter baumannii.