上海医学
上海醫學
상해의학
SHANGHAI MEDICAL JOURNAL
2009年
11期
987-991,插1
,共6页
谢伟霖%蒋更如%尤新民%陈治宇%阮正上
謝偉霖%蔣更如%尤新民%陳治宇%阮正上
사위림%장경여%우신민%진치우%원정상
多器官功能障碍综合征%N-乙酰半胱氨酸%核因子-kB
多器官功能障礙綜閤徵%N-乙酰半胱氨痠%覈因子-kB
다기관공능장애종합정%N-을선반광안산%핵인자-kB
Multiple organ dysfunction syndrome%N-acetylcysteine%Nuclear factor-kappa B
目的 通过观察N-乙酰半胱氨酸(NAC)对多器官功能障碍综合征(MODS)大鼠的器官功能、核因子(NF)-kB、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6的影响,探讨NAC对MODS的器官保护作用及其机制.方法 将35只Sprague-Dawley大鼠分为假手术对照(Sham)组(5只)、MODS组(15只)、MODS+NAC组(15只).用肠缺血/再灌注结合酵母多糖腹腔注射制作成MODS大鼠动物模型,动脉夹夹闭肠系膜上动脉45 min,然后松夹恢复灌注,在恢复灌注12 h后,腹腔注射酵母多糖与0.9%氯化钠溶液混悬液(250 mg/kg).MODS+NAC组在恢复再灌注时,注射NAC 150 mg/kg.于注射酵母多糖18 h后,测定大鼠的动脉血氧分压(PaO_2)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、尿素氮(BUN)、肌酐(Cr)、肌酸激酶(CK),取肝、肾组织,应用凝胶迁移率法检测NF-kB的活性,酶联免疫吸附试验检测大鼠的血清TNF-α、IL-6含量,留肺、肝脏、肾、小肠标本行病理组织学检查.结果 MODS组大鼠的PaO_2较Sham组大鼠显著降低(P<0.01),而MODS+NAC组大鼠的PaO_2较MODS组大鼠显著升高(P<0.01).MODS组大鼠的ALT、AST、TBIL、BUN、Cr、CK均较Sham组显著升高(P值均<0.01),而MODS+NAC组大鼠上述指标较MODS组大鼠显著降低(P值均<0.01).MODS组大鼠的血清TNF-α、IL-6含量较Sham组显著升高(P值均<0.01),而MODS+NAC组则较MODS组大鼠显著降低(P值均<0.01).MODS组大鼠的肝脏、肾脏NF-kB活性均较Sham组显著升高(P值均<0.01),而MODS+NAC组则较MODS组显著降低(P值均<0.01).Sham组大鼠肺、肝脏、肾脏及小肠的病理表现基本正常,MODS组大鼠各器官存在明显的病理损伤,而MODS+NAC组的病理损伤程度较MODS组有所好转.结论 应用NAC可以对MODS大鼠起到器官保护作用,其机制可能与抑制NF-kB活性从而减少炎性因子合成有关.
目的 通過觀察N-乙酰半胱氨痠(NAC)對多器官功能障礙綜閤徵(MODS)大鼠的器官功能、覈因子(NF)-kB、腫瘤壞死因子(TNF)-α、白細胞介素(IL)-6的影響,探討NAC對MODS的器官保護作用及其機製.方法 將35隻Sprague-Dawley大鼠分為假手術對照(Sham)組(5隻)、MODS組(15隻)、MODS+NAC組(15隻).用腸缺血/再灌註結閤酵母多糖腹腔註射製作成MODS大鼠動物模型,動脈夾夾閉腸繫膜上動脈45 min,然後鬆夾恢複灌註,在恢複灌註12 h後,腹腔註射酵母多糖與0.9%氯化鈉溶液混懸液(250 mg/kg).MODS+NAC組在恢複再灌註時,註射NAC 150 mg/kg.于註射酵母多糖18 h後,測定大鼠的動脈血氧分壓(PaO_2)、丙氨痠轉氨酶(ALT)、天鼕氨痠轉氨酶(AST)、總膽紅素(TBIL)、尿素氮(BUN)、肌酐(Cr)、肌痠激酶(CK),取肝、腎組織,應用凝膠遷移率法檢測NF-kB的活性,酶聯免疫吸附試驗檢測大鼠的血清TNF-α、IL-6含量,留肺、肝髒、腎、小腸標本行病理組織學檢查.結果 MODS組大鼠的PaO_2較Sham組大鼠顯著降低(P<0.01),而MODS+NAC組大鼠的PaO_2較MODS組大鼠顯著升高(P<0.01).MODS組大鼠的ALT、AST、TBIL、BUN、Cr、CK均較Sham組顯著升高(P值均<0.01),而MODS+NAC組大鼠上述指標較MODS組大鼠顯著降低(P值均<0.01).MODS組大鼠的血清TNF-α、IL-6含量較Sham組顯著升高(P值均<0.01),而MODS+NAC組則較MODS組大鼠顯著降低(P值均<0.01).MODS組大鼠的肝髒、腎髒NF-kB活性均較Sham組顯著升高(P值均<0.01),而MODS+NAC組則較MODS組顯著降低(P值均<0.01).Sham組大鼠肺、肝髒、腎髒及小腸的病理錶現基本正常,MODS組大鼠各器官存在明顯的病理損傷,而MODS+NAC組的病理損傷程度較MODS組有所好轉.結論 應用NAC可以對MODS大鼠起到器官保護作用,其機製可能與抑製NF-kB活性從而減少炎性因子閤成有關.
목적 통과관찰N-을선반광안산(NAC)대다기관공능장애종합정(MODS)대서적기관공능、핵인자(NF)-kB、종류배사인자(TNF)-α、백세포개소(IL)-6적영향,탐토NAC대MODS적기관보호작용급기궤제.방법 장35지Sprague-Dawley대서분위가수술대조(Sham)조(5지)、MODS조(15지)、MODS+NAC조(15지).용장결혈/재관주결합효모다당복강주사제작성MODS대서동물모형,동맥협협폐장계막상동맥45 min,연후송협회복관주,재회복관주12 h후,복강주사효모다당여0.9%록화납용액혼현액(250 mg/kg).MODS+NAC조재회복재관주시,주사NAC 150 mg/kg.우주사효모다당18 h후,측정대서적동맥혈양분압(PaO_2)、병안산전안매(ALT)、천동안산전안매(AST)、총담홍소(TBIL)、뇨소담(BUN)、기항(Cr)、기산격매(CK),취간、신조직,응용응효천이솔법검측NF-kB적활성,매련면역흡부시험검측대서적혈청TNF-α、IL-6함량,류폐、간장、신、소장표본행병리조직학검사.결과 MODS조대서적PaO_2교Sham조대서현저강저(P<0.01),이MODS+NAC조대서적PaO_2교MODS조대서현저승고(P<0.01).MODS조대서적ALT、AST、TBIL、BUN、Cr、CK균교Sham조현저승고(P치균<0.01),이MODS+NAC조대서상술지표교MODS조대서현저강저(P치균<0.01).MODS조대서적혈청TNF-α、IL-6함량교Sham조현저승고(P치균<0.01),이MODS+NAC조칙교MODS조대서현저강저(P치균<0.01).MODS조대서적간장、신장NF-kB활성균교Sham조현저승고(P치균<0.01),이MODS+NAC조칙교MODS조현저강저(P치균<0.01).Sham조대서폐、간장、신장급소장적병리표현기본정상,MODS조대서각기관존재명현적병리손상,이MODS+NAC조적병리손상정도교MODS조유소호전.결론 응용NAC가이대MODS대서기도기관보호작용,기궤제가능여억제NF-kB활성종이감소염성인자합성유관.
Objective To observe the influence of N-acetylcysteine(NAC)on nuclear factor-kappa B (NF-kB),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in rats with multiple organ dysfunction syndrome (MODS),so as to discuss the protective effect of NAC against MODS and the related mechanism.Methods Thirty-five Sprague-Dawley rats were randomly divided into sham group(n=5),MODS group(n=15)and MODS+NAC group(n=15).The rat MODS model was established by intestinal ischemia-reperfusion(I/R)combined with intraperitoneal injection of zymosan. In the MODS and MODS+NAC groups,the superior mesenteric arteries(SMA)of rats were occluded for 45 min and reperfused for 12 h,and then zymosan (250 mg/kg I.p.)was administered.NAC(150 mg/kg I.v.)was given immediately after reperfusion in the MODS+NAC group.Eighteen hours after the injection of zymosan,blood and tissue samples were collected from each group.Then the pathomorphological and functional changes of the lung,heart,liver and kidney tissues (including pressure of arterial oxygen[PaO_2],alanine aminotransferase[ALT],aspartate aminotransferase [AST],total bilirubin[TBIL],blood urea nitrogen[BUN],creatinine [Cr],and creatine kinase[CK])were observed. Serum TNF-α and IL-6 concentrations were detected by enzyme linked immunosorbent assay (ELISA).The activities of NF-kB in the liver and kidney tissues were examined by electrophoretic mobility shift assay (EMSA). Results The PaO_2 in the MODS group was significantly lower than those in the sham operation group and the MODS+ NAC group (both P<0. 01 ). The serum levels of ALT, AST, TBIL, BUN, Cr, and OK in the MODS group were significantly higher than those in the sham group and the MODS+ NAC group (all P<0.01).The serum levels of IL-6 and TNF-α in the MODS group were significantly higher than those in the sham group and the MODS+ NAC group (all P<0. 01 ). The activities of NF-kB in the liver and kidney in the MODS group were significantly higher than those in the sham group and the MODS+ NAC group (all P<0. 01 ). The pathology of the lung, liver, and kidney was nearly normal in the sham group, and rats in the MODS group had obvious injuries of different organs. The pathologic lesions in the lung, kidney, liver, and intestine tissues in the MODS+ NAC group were milder than those in the MODS group. Conclusion NAC has an organ protective effect on MODS rats, and the mechanism might be associated with the inhibition of NF-kB activity and the subsequent decrease of inflammatory responses.
