中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2010年
1期
9-14
,共6页
蔡露良%向伟%谢耀琦%廖锋%冯小伟%张笃飞%陈玉雯%张亚明%黄美娇%曾霞
蔡露良%嚮偉%謝耀琦%廖鋒%馮小偉%張篤飛%陳玉雯%張亞明%黃美嬌%曾霞
채로량%향위%사요기%료봉%풍소위%장독비%진옥문%장아명%황미교%증하
白细胞介素-8%基因%脓毒症
白細胞介素-8%基因%膿毒癥
백세포개소-8%기인%농독증
Interleukin-18%Gene polymorphism%Sepsis
目的 研究白细胞介素(IL-18)基因启动子多态性位点以及相应血清IL-18含量与儿童脓毒症(Sepsis)的关系.方法 双抗体夹心酶联免疫吸附实验(ELISA)法、聚合酶链反应-序列特异性引物(PCR-SSP)和测序的方法 .两组间比较采用t检验,多组间比较采用方差分析,计数资料比较采用χ~2检验.结果 ①脓毒症患儿血清IL-18水平为(196.56±157.32)pg/ml,明显高于健康儿童的(66.16±41.63)PS/ml(P<0.01),随着脓毒症患儿病情的加重,血清IL-18浓度呈上升趋势,非危重组[(152.87±114.96)pg/ml]明显高于对照组[(66.16±41.63)pg/ml],危重组[(191.98±169.72)pg/ml]高于非危重组,极危重组血清IL-18浓度[(323.89±159.35)pg/ml]显著增高,差异有非常显著性(P=0.000),各组间比较差异均有显著性(P<0.01),相关分析发现血IL-18水平与小儿危重病例评分呈负相关(P<0.01).②健康儿童与脓毒症患儿均存在IL-18基因启动子多态性.健康儿童和脓毒症患儿-137G/C基因型频率分别为GG型(61.8%)、GC型(35.8%)、CC型(2.4%)和GG型(71.1%)、GC型(26.7%)、CC型(2.2%);等位基因的频率分别为G型(79.7%)和G型(84.4%).健康儿童和脓毒症患儿-60TC/A基因型频率分别为CA型(61.0%)、CC型(26.8%)、AA型(12.2%)和CA型(76.7%)、CC型(21.1%)、AA型(2.2%);等位基因的频率分别为C型(57.3%)和C型(59.4%).③脓毒症患儿-607CA基因型分布频率(76.7%)显著高于健康儿童(61.0%),AA基因型分布频率(2.2%)显著低于健康儿童(12.2%),差异均有显著性(P<0.05).④依-137CC、-137GC、-137GG顺序,健康儿童血清IL-18水平分别为:(45.67±28.36)pg/ml、(53.27±37.91)pg/ml、(76.91±42.44)pg/ml;而脓毒症患儿分别为:(140.50±60.10)pg/ml、(184.42±157.33)pg/ml、(237.02±161.76)pg/ml.依-607AA、-607CA、-607CC顺序,健康儿童血清IL-18水平分别为:(48.80±32.11)pg/ml、(68.41±42.53)ps/ml、(70.17±43.87)pg/ml;而脓毒症患儿分别为:(141.50±64.35)pg/ml、(151.21±121.19)pg/ml、(211.16±163.64)pg/ml.但差异无统计学意义(P>0.05).结论 脓毒症患儿血清IL-18水平明显升高,且与病情的加重有关.IL-18基因启动子-607CA基因型携带者儿童更易罹患脓毒症,表明-607CA基因型可能为脓毒症易感基因型,而-607AA基因型可能对儿童患脓毒症具有对抗作用.
目的 研究白細胞介素(IL-18)基因啟動子多態性位點以及相應血清IL-18含量與兒童膿毒癥(Sepsis)的關繫.方法 雙抗體夾心酶聯免疫吸附實驗(ELISA)法、聚閤酶鏈反應-序列特異性引物(PCR-SSP)和測序的方法 .兩組間比較採用t檢驗,多組間比較採用方差分析,計數資料比較採用χ~2檢驗.結果 ①膿毒癥患兒血清IL-18水平為(196.56±157.32)pg/ml,明顯高于健康兒童的(66.16±41.63)PS/ml(P<0.01),隨著膿毒癥患兒病情的加重,血清IL-18濃度呈上升趨勢,非危重組[(152.87±114.96)pg/ml]明顯高于對照組[(66.16±41.63)pg/ml],危重組[(191.98±169.72)pg/ml]高于非危重組,極危重組血清IL-18濃度[(323.89±159.35)pg/ml]顯著增高,差異有非常顯著性(P=0.000),各組間比較差異均有顯著性(P<0.01),相關分析髮現血IL-18水平與小兒危重病例評分呈負相關(P<0.01).②健康兒童與膿毒癥患兒均存在IL-18基因啟動子多態性.健康兒童和膿毒癥患兒-137G/C基因型頻率分彆為GG型(61.8%)、GC型(35.8%)、CC型(2.4%)和GG型(71.1%)、GC型(26.7%)、CC型(2.2%);等位基因的頻率分彆為G型(79.7%)和G型(84.4%).健康兒童和膿毒癥患兒-60TC/A基因型頻率分彆為CA型(61.0%)、CC型(26.8%)、AA型(12.2%)和CA型(76.7%)、CC型(21.1%)、AA型(2.2%);等位基因的頻率分彆為C型(57.3%)和C型(59.4%).③膿毒癥患兒-607CA基因型分佈頻率(76.7%)顯著高于健康兒童(61.0%),AA基因型分佈頻率(2.2%)顯著低于健康兒童(12.2%),差異均有顯著性(P<0.05).④依-137CC、-137GC、-137GG順序,健康兒童血清IL-18水平分彆為:(45.67±28.36)pg/ml、(53.27±37.91)pg/ml、(76.91±42.44)pg/ml;而膿毒癥患兒分彆為:(140.50±60.10)pg/ml、(184.42±157.33)pg/ml、(237.02±161.76)pg/ml.依-607AA、-607CA、-607CC順序,健康兒童血清IL-18水平分彆為:(48.80±32.11)pg/ml、(68.41±42.53)ps/ml、(70.17±43.87)pg/ml;而膿毒癥患兒分彆為:(141.50±64.35)pg/ml、(151.21±121.19)pg/ml、(211.16±163.64)pg/ml.但差異無統計學意義(P>0.05).結論 膿毒癥患兒血清IL-18水平明顯升高,且與病情的加重有關.IL-18基因啟動子-607CA基因型攜帶者兒童更易罹患膿毒癥,錶明-607CA基因型可能為膿毒癥易感基因型,而-607AA基因型可能對兒童患膿毒癥具有對抗作用.
목적 연구백세포개소(IL-18)기인계동자다태성위점이급상응혈청IL-18함량여인동농독증(Sepsis)적관계.방법 쌍항체협심매련면역흡부실험(ELISA)법、취합매련반응-서렬특이성인물(PCR-SSP)화측서적방법 .량조간비교채용t검험,다조간비교채용방차분석,계수자료비교채용χ~2검험.결과 ①농독증환인혈청IL-18수평위(196.56±157.32)pg/ml,명현고우건강인동적(66.16±41.63)PS/ml(P<0.01),수착농독증환인병정적가중,혈청IL-18농도정상승추세,비위중조[(152.87±114.96)pg/ml]명현고우대조조[(66.16±41.63)pg/ml],위중조[(191.98±169.72)pg/ml]고우비위중조,겁위중조혈청IL-18농도[(323.89±159.35)pg/ml]현저증고,차이유비상현저성(P=0.000),각조간비교차이균유현저성(P<0.01),상관분석발현혈IL-18수평여소인위중병례평분정부상관(P<0.01).②건강인동여농독증환인균존재IL-18기인계동자다태성.건강인동화농독증환인-137G/C기인형빈솔분별위GG형(61.8%)、GC형(35.8%)、CC형(2.4%)화GG형(71.1%)、GC형(26.7%)、CC형(2.2%);등위기인적빈솔분별위G형(79.7%)화G형(84.4%).건강인동화농독증환인-60TC/A기인형빈솔분별위CA형(61.0%)、CC형(26.8%)、AA형(12.2%)화CA형(76.7%)、CC형(21.1%)、AA형(2.2%);등위기인적빈솔분별위C형(57.3%)화C형(59.4%).③농독증환인-607CA기인형분포빈솔(76.7%)현저고우건강인동(61.0%),AA기인형분포빈솔(2.2%)현저저우건강인동(12.2%),차이균유현저성(P<0.05).④의-137CC、-137GC、-137GG순서,건강인동혈청IL-18수평분별위:(45.67±28.36)pg/ml、(53.27±37.91)pg/ml、(76.91±42.44)pg/ml;이농독증환인분별위:(140.50±60.10)pg/ml、(184.42±157.33)pg/ml、(237.02±161.76)pg/ml.의-607AA、-607CA、-607CC순서,건강인동혈청IL-18수평분별위:(48.80±32.11)pg/ml、(68.41±42.53)ps/ml、(70.17±43.87)pg/ml;이농독증환인분별위:(141.50±64.35)pg/ml、(151.21±121.19)pg/ml、(211.16±163.64)pg/ml.단차이무통계학의의(P>0.05).결론 농독증환인혈청IL-18수평명현승고,차여병정적가중유관.IL-18기인계동자-607CA기인형휴대자인동경역리환농독증,표명-607CA기인형가능위농독증역감기인형,이-607AA기인형가능대인동환농독증구유대항작용.
Objectlve To investigate the correlations of serum interleukin-18(IL-18)level and IL-18 gene promoter polymorphisms to the development of sepsis in children.Method Using enzyme-linked immunosorbent assay(ELISA),the authors tested the serum IL-18 level in 90 patients with sepsis and 123 normal controls,and their single nucleotide polymorphisms of the promoter region of IL-18 gene at position-607C/A and-137G/C were detected using polymerase chain reaction with sequence specific primers method and sequencing technique.Result ① The serum IL-18 level in sepsis groups was(196.56±157.32) pg/ml that was significantly higher than(66.16±41.63)pg/ml in normal controls(P<0.01),the more severe the degree of sepsis wag.the more significantly higher the serum IL-18 level was.The serum IL-18 level in non serious sepsis group was ( 152. 87±114. 96) pg/ml that was significantly higher than (66. 16 ±41.63) pg/ml in normal controls, the serum IL-18 level in serious sepsis group was (191.98±169. 72)pg/ml that was significantly higher than that in non serious sepsis group, and the serum IL-18 level in extremely serious sepsis patients was ( 323.89±159. 35 ) pg/ml, the difference was highly significant ( P = 0. 000). The difference was significant among the groups with different severity of sepsis( P <0. 01 ). There was a negative correlation between PCIS (pediatric critical illness score) of sepsis and the serum IL-18 level (P<0.01). ②There were polymorphisms in IL-18 gene promoter of matched healthy children and sepsis in children. The GG genotype frequency (61.8%) of IL-18-137G/C in healthy children was the highest, followed by GC genotype (35. 8% ) and CC genotype (2. 4% ) in sequence. The G allele frequency (79. 7% ) was higher in IL-18-137G/C of healthy children than C allele (20. 3% ). The GG genotype frequency (71.1%) of IL-18-137G/C in septic children was the highest, the next were GC genotype (26. 7% ) and CC genotype (2. 2% ). The G allele frequency (84.4%) was higher in IL-18-137G/C of septic children than C allele ( 15.6% ). The CA genotype frequency (61.0%) of IL-18-607C/A in healthy children was the highest, followed by CC genotype ( 26. 8% ) and AA genotype ( 12. 2% ). The C allele frequency (57.3%) was higher in IL-18-607C/A of healthy children than A allele (42. 7% ). The CA genotype frequency (76. 7% ) of IL-18-607C/A in septic children was the highest, followed by CC genotype (21.1%) and AA genotype (2. 2% ) in sequence. The C allele frequency (59.4%) was higher in IL-18- 607 C/A of septic chidren than A allele (40.6%).③ The genotype frequency of IL-18-607 CA was 76.7% in sepsis groups that was significantly higher than 61.0% in normal controls, and the genotype frequency of -607 AA was 2. 2% in sepsis groups that was significantly lower than 12. 2% in normal controls, the difference was significant (P<0.05).④In the order of-137CC,-137GC,-137GG,the serum IL-18 level in normal controls were as follows : (45.67 ± 28. 36) pg/ml, ( 53.27 ± 37.91 ) pg/ml, ( 76.91 ± 42.44 )pg/ml, and with (140.50 ±60.10) pg/ml, (184.42 ± 157.33) pg/ml, (237.02 ± 161.76) pg/ml respectively in sepsis groups. In the order of -607AA, -607CA, -607CC, the serum IL-18 level in normal controls were : ( 48. 80 ± 32. 11 ) pg/ml, ( 68.41 ± 42. 53 ) pg/ml, ( 70. 17 ± 43.87 ) pg/ml ; and with (141.50±64.35) pg/ml, (151.21 ± 121.19) pg/nd, (211.16 ± 163.64) pg/ml respectively in sepsis groups. The difference was not significant among different groups( P > 0. 05 ). Conclusion The serum IL-18 level in sepsis groups was significantly higher than that in normal controls, which was related to the severity of sepsis. It was possible that the genotype of-607CA carriers was susceptible to sepsis, which mean that the genotype of -607CA might be susceptible genotype of sepsis. However, the genotype of -607AA might play an oppose role in the risk of sepsis.
