国际呼吸杂志
國際呼吸雜誌
국제호흡잡지
INTERNATIONAL JOURNAL OF RESPIRATION
2010年
12期
705-708,封3
,共5页
梁艳%吴雪琼%张俊仙%李宁%阳幼荣%余琦%宋晶莹%李忠明%王博%安慧茹%史迎昌%白雪娟%刘成龙
樑豔%吳雪瓊%張俊仙%李寧%暘幼榮%餘琦%宋晶瑩%李忠明%王博%安慧茹%史迎昌%白雪娟%劉成龍
량염%오설경%장준선%리저%양유영%여기%송정형%리충명%왕박%안혜여%사영창%백설연%류성룡
结核分枝杆菌%DNA疫苗%耐多药结核病
結覈分枝桿菌%DNA疫苗%耐多藥結覈病
결핵분지간균%DNA역묘%내다약결핵병
Mycobacterium tuberculosis%DNA vaccine%Multi-drug resistant tuberculosis
目的 研究结核分枝杆菌Ag85A质粒DNA疫苗单独或联合药物治疗小鼠耐多药结核病的效果,为建立耐多药结核病的免疫治疗新策略和新方案奠定基础.方法 用结核分枝杆菌高耐利福平、低耐异烟肼临床分离株HB361尾静脉注射17～19 g的6～8周龄雌性BALB/C小鼠后,将小鼠随机分为6组,每组10只.感染后第2天开始,分别用pVAX1载体(A组)、利福平(B组)、吡嗪酰胺(C组)、Ag85A质粒DNA疫苗(D组)、Ag85A质粒DNA疫苗联合利福平(E组)、Ag85A质粒DNA疫苗联合吡嗪酰胺(F组)治疗60 d.治疗结束后4周,分别取肺、肝和脾观察病理改变,称取重量,做菌落计数.结果 小鼠感染4周后,肺内菌量达到1.5×107 CFU,脾内菌量达到1.1×106 CFU.A、B组小鼠死亡率均为10%,其余各组小鼠均存活.治疗结束后4周,肺组织病理显示,各治疗组肺组织病变均有不同程度减轻,病变局限,可见正常的肺泡结构,肺泡轮廓相对清晰.与A组比较,C、D、E、F组肺组织菌落数分别减少了1.18、1.35、1.38、1.08 logs,脾脏菌落数分别减少了0.91、1.00、1.26、1.03 logs(P＜0.01).结论 结核分枝杆菌Ag85A质粒DNA疫苗单独或联合药物治疗小鼠耐多药结核病均有显著疗效.Ag85A质粒DNA疫苗与抗结核药物联合治疗是治疗耐多药结核病的最有前途的免疫策略.
目的 研究結覈分枝桿菌Ag85A質粒DNA疫苗單獨或聯閤藥物治療小鼠耐多藥結覈病的效果,為建立耐多藥結覈病的免疫治療新策略和新方案奠定基礎.方法 用結覈分枝桿菌高耐利福平、低耐異煙肼臨床分離株HB361尾靜脈註射17～19 g的6～8週齡雌性BALB/C小鼠後,將小鼠隨機分為6組,每組10隻.感染後第2天開始,分彆用pVAX1載體(A組)、利福平(B組)、吡嗪酰胺(C組)、Ag85A質粒DNA疫苗(D組)、Ag85A質粒DNA疫苗聯閤利福平(E組)、Ag85A質粒DNA疫苗聯閤吡嗪酰胺(F組)治療60 d.治療結束後4週,分彆取肺、肝和脾觀察病理改變,稱取重量,做菌落計數.結果 小鼠感染4週後,肺內菌量達到1.5×107 CFU,脾內菌量達到1.1×106 CFU.A、B組小鼠死亡率均為10%,其餘各組小鼠均存活.治療結束後4週,肺組織病理顯示,各治療組肺組織病變均有不同程度減輕,病變跼限,可見正常的肺泡結構,肺泡輪廓相對清晰.與A組比較,C、D、E、F組肺組織菌落數分彆減少瞭1.18、1.35、1.38、1.08 logs,脾髒菌落數分彆減少瞭0.91、1.00、1.26、1.03 logs(P＜0.01).結論 結覈分枝桿菌Ag85A質粒DNA疫苗單獨或聯閤藥物治療小鼠耐多藥結覈病均有顯著療效.Ag85A質粒DNA疫苗與抗結覈藥物聯閤治療是治療耐多藥結覈病的最有前途的免疫策略.
목적 연구결핵분지간균Ag85A질립DNA역묘단독혹연합약물치료소서내다약결핵병적효과,위건립내다약결핵병적면역치료신책략화신방안전정기출.방법 용결핵분지간균고내리복평、저내이연정림상분리주HB361미정맥주사17～19 g적6～8주령자성BALB/C소서후,장소서수궤분위6조,매조10지.감염후제2천개시,분별용pVAX1재체(A조)、리복평(B조)、필진선알(C조)、Ag85A질립DNA역묘(D조)、Ag85A질립DNA역묘연합리복평(E조)、Ag85A질립DNA역묘연합필진선알(F조)치료60 d.치료결속후4주,분별취폐、간화비관찰병리개변,칭취중량,주균락계수.결과 소서감염4주후,폐내균량체도1.5×107 CFU,비내균량체도1.1×106 CFU.A、B조소서사망솔균위10%,기여각조소서균존활.치료결속후4주,폐조직병리현시,각치료조폐조직병변균유불동정도감경,병변국한,가견정상적폐포결구,폐포륜곽상대청석.여A조비교,C、D、E、F조폐조직균락수분별감소료1.18、1.35、1.38、1.08 logs,비장균락수분별감소료0.91、1.00、1.26、1.03 logs(P＜0.01).결론 결핵분지간균Ag85A질립DNA역묘단독혹연합약물치료소서내다약결핵병균유현저료효.Ag85A질립DNA역묘여항결핵약물연합치료시치료내다약결핵병적최유전도적면역책략.
Objective To establish foundation for new strategy and program on immune therapy of multi-drug resistant tuberculosis (MDR-TB) by studying the therapeutic effects of Mycobacterium tuberculosis Ag85A plasmid DNA vaccine alone or combined with drugs on MDR-TB mice. Methods Sixty 6-8 weeks old female BALB/C mice were injected via tail vein with clinical isolate Mycobacterium tuberculosis HB361 which was highly resistant to rifampin (RFP) and lowly resistant to isoniazid. The mice were randomly divided into six groups, ten mice in each group. From the second day after infection,the mice respectively received pVAX1 vector (group A), RFP (group B), pyrazinamide (PZA) (group C),Ag85A plasmid DNA vaccine (group D), Ag85A plasmid DNA vaccine combined with RFP (group E),Ag85A plasmid DNA vaccine combined with PZA (group F) for sixty days. Four weeks after the end of treatment,the lung, liver and spleen of the mice were taken and their pathological changes, weight and colony count were examined. Results Four weeks after infection, the numbers of bacteria in lung and spleen of the mice reached up to 1.5×107 CFU and 1.1 × 106 CFU,respectively. The death rates of mice in group A and group B were both 10% ,and the mice in other groups were alive. Four weeks after the end of treatment,lung pathology in the treated groups showed that the lung lesions were slight and limited,normal alveolar structure were seen, and the profile of the alveoli was relatively clear. Compared with group A, group C, D, E, F reduced by 1.18,1.35,1.38,1.08 logs on the colony count of lung, and reduced by 0.91,1.00,1.26 and 1.03 logs on the colony count of spleen (P＜0.01), respectively. Conclusions Mycobacterium tuberculosis Ag85A plasmid DNA vaccine alone or combined with drugs has significant therapeutic effects on MDR-TB mice. Ag85A plasmid DNA vaccine combined with anti-tuberculosis drugs is the most promising immunization strategy for treatment of MDR-TB.
