LPS诱导的内毒素血症小鼠及重症联合免疫缺陷小鼠模型炎症反应的比较

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文章编号:1007-8738(2011)01-0044-03

LPS 诱导的内毒素血症小鼠及重症联合免疫缺陷小鼠模型炎症反应的比较

罗 冲,杨锡强*,李 欣,刘 玮,王莉佳

(重庆医科大学附属儿童医院儿童发育疾病研究省部共建教育部重点实验室,重庆400014)

收稿日期:2010-07-14; 接受日期:2010-09-13基金项目:国家自然科学基金资助项目(30772915)作者简介:罗 冲(1981-),女,四川成都人,在读博士

T e:l 023 ********;E m ai:l l uochong @yahoo .c n

*Correspond i ng au t hor ,E m ai:l x i qyang @163.co m

Co mparation of i nfl a mm ation bet w een

w il d m ice and severe co m bi ned i m m u nodeficiency m ice w ith endotoxe m ia i n duced by li popo l ysacchari de

LUO Chong,Y ANG X i qiang *,L I X i n ,

LIU W ei ,

WANG L i ji a ng

M i n i stry o f Educati on K ey L aboratory of Chil d D ev elopment and D i so rders ,Ch ildren s H o spita,l Chongq i ng M ed ica l U niversity ,Chongqi ng 400014,China

[Abstract] A I M:To compa re t he in flamma tion be t w een

w ild BALB /c m ice and m ice w ith seve re comb ined m i muno

de ficiency (SC I D )w ith endo toxem ia i n duced by lipopo lysacchar i d e (LPS ).METHODS :Endo t oxem ia m ode ls o f w ild and SC I D m ice we re estab lished by in jecti n g LPS intra pe ritonea lly .S eru m was taken be fore and 3h ,6h ,12h a f t e r in jecting LPS,live r and lung were t aken 12h a fter in j e c ting LPS.A lan i n e transa rn inase (A LT ),a spa rtate am in o transf e rase (AST)and b lood u rea n itrogen (BUN)l e ve ls we re mea sured by automa tic b iochem ica l ana lyz e r .L ive r and lung in flamma tion in jury we re observed by H .E s t a i n ing .TNF ,I FN ,IL 6and MCP 1leve ls in se rum we re detect ed by Cyt ome tr ic Bead A rray (CBA ).RESULTS :(1)A ll o fSC I D m ice (8/8)we re dead a t 12-24h a ft e r in jecting LPS ,and on ly one BALB /c mouse (1/8)was dead .(2)A LT and AST leve ls o f SC I D m ice 12h a fter in j e cting LPS we re h iger than those of BALB /c m ice (P <0.05),bu t the re was no d iff e rence o f BUN l e ve ls be t w een them.(3)The b li n d live r and lung pa tho logy score s o f SC I D m ice we re h ighe r than those o f BALB /c m ice (P <0.05).(4)TNF ,I FN ,IL 6and MCP 1l e ve ls in seru m a t 3h ,6h ,12h a f t e r in j e c ting LPS increased significan tly ,and t he cy t okine leve ls o f SC I D m ice w ere h igher t han t hose o f BA LB /c m ice (P <0.05).CONCLUSI ON :SC I D m ice don t on ly exce s sive ly secre te infla mma t o ry cytokines a fter in j e c ting LPS,but a lso lead t o m ore seve re endo toxem ia and infla mma tion in jury o f o rgans ,wh ich a re the m i portan t cause o f mouse

dea t h .The above resu lt s a lso show t ha t the ad j u st men t de fi c i e ncy o f adap tive m i m uno response ,abnor m a l augmen t a

ti o n o f innate m i munore sponse may be an m i portan t cause o f seve re S I RS of endange ring life .[K ey word s]

li p opo lysacchar i d e ;seve re comb ined m i m uno de ficiency ;in flamma ti o n reaction ;mouse

[摘要] 目的:比较脂多糖(LPS)诱导的内毒素血症BALB /c 小鼠及重症联合免疫缺陷(SCID )小鼠炎症反应的差异。方法:建立LPS 诱导的BALB /c 小鼠和SC I D 小鼠内毒素血症模型,观察小鼠的存活率。分别于诱导前、诱导后3h 、6h 、12h ,取小鼠的血清及诱导后12h 小鼠的肝脏、肺脏,用全自动生化分析仪检测两种小鼠血清谷丙转氨酶(A LT )、谷草转氨酶(A ST )、尿素氮(BUN )水平;HE 染色评价肝脏、肺脏的炎症病理改变;用流式细胞术微球阵列法检测两种小鼠血清TNF 、IFN 、I L 6及M CP 1的水平。结果:(1)LPS 诱导内毒素血症后,SC I D 小鼠于12~24h 均死亡(8/8),BA LB /c 小鼠仅1只死亡(1/8)。(2)LPS 诱导后12h ,BALB /c 小鼠及SCID 小鼠血清ALT 、AST 、BUN 的水平均明显升高(P <0.05),SC I D 小鼠前两项均高于B A LB /c 小鼠(P <0.05),但B UN 两种小鼠无显著差异。(3)肺脏,肝脏炎症盲法的病理评分,SC I D 小鼠均高于BALB /c 小鼠(P <0.05)。(4)SC I D 小鼠和BALB /c 小鼠LPS 诱导后3h 、6h 、12h ,血清TN F ,I FN 的水平,诱导后12h ,IL 6,M CP 1的水平均显著升高(P <0.05),SC I D 小鼠明显高于BALB /c 小鼠(P <0.05)。结论:LPS 刺激SC I D 小鼠后,可分泌过量的炎性细胞因子,导致更严重的内毒素血症和脏器损伤,是造成小鼠死亡的重要原因。结果提示,缺乏适应性免疫应答细胞调控的情况下,异常增强的固有免疫应答,可能是危及机体生命的重症全身炎症反应综合征发生的重要原因。

[关键词]脂多糖;重症联合免疫缺陷;炎症反应;小鼠[中图分类号]R392.1

[文献标识码]A

脓毒症、重症急性呼吸窘迫综合征(severe acute resp iratory syndro m e ,SARS)及感染相关的嗜血细胞综合征(infection associated he m ophagocy tic syndro m e ,I A H S)均为机体全身炎症反应的表现[1-2]

。失控的

炎症反应可导致机体多器官功能障碍引起死亡,给临床治疗带来极大困难,是以上疾病预后不良的重要原因。目前认为,I A H S 是由于感染引起的T 细胞及单核巨噬细胞过度活化所致,但对于脓毒症、SARS 的免疫病理以及固有免疫应答与适应性免疫应