中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2012年
10期
612-615
,共4页
普通肝素%内毒素%急性肺损伤%凝血%炎症%组织学评分
普通肝素%內毒素%急性肺損傷%凝血%炎癥%組織學評分
보통간소%내독소%급성폐손상%응혈%염증%조직학평분
Unfractioned heparin%Endotoxin%Acute lung injury%Coagulation%Inflammation%Histology score
目的 通过比较雾化吸入不同剂量普通肝素(UFH)对内毒素致急性肺损伤(ALI)大鼠肺部凝血、炎症和肺损伤组织学的效应,探讨UFH局部给药干预肺内凝血病的合适剂量.方法 29只雄性Wistar大鼠经尾静脉注射大肠杆菌脂多糖(LPS)复制ALI模型,按随机数字表法分为对照组(5只)和UFH组(24只).UFH组于制模后2h分别给予6、12、18 U/g的UFH 10 ml雾化吸入1次实施干预,而对照组则仅用生理盐水进行雾化吸入.LPS注射后6h处死大鼠,进行肺泡灌洗,收集支气管肺泡灌洗液(BALF).采用酶联免疫吸附试验( ELISA)检测凝血酶-抗凝血酶复合物(TATc)、肿瘤坏死因子-α(TNF-α)水平；计算肺组织湿/干重(W/D)比值,并进行肺损伤病理评分.结果 UFH 6 U/g和12 U/g组BALF中TATc(μg/L)、TNF-α(ng/L)以及肺组织W/D比值、病理评分(分)均明显低于对照组(TATc:0.959±0.681、1.165±0.854比2.141±0.791,TNF-α:4.449±5.054、9.096±4.099比18.184±3.869,W/D比值:7.018±1.137、7.367±0.349比8.472±0.614,病理评分:16.0±1.0、16.5±1.5比19.6±0.4,P＜0.05或P＜0.01).UFH不同剂量组间BALF中TATc水平和病理评分无差异；UFH 18 U/g组BALF中TNF-α明显高于UFH 6 U/g组(15.503±8.753比4.449±5.054,P＜0.01)；UFH18 U/g组肺组织W/D比值明显高于UFH 6 U/g组(8.850±1.157比7.018±1.137,P＜0.05)和12 U/g组(8.850±1.157比7.367±0.349,P＜0.05).结论 雾化吸入不超过12 U/g剂量的UFH治疗ALI时,能够抑制肺泡局部高凝状态,减轻早期炎症反应和肺组织损伤.
目的 通過比較霧化吸入不同劑量普通肝素(UFH)對內毒素緻急性肺損傷(ALI)大鼠肺部凝血、炎癥和肺損傷組織學的效應,探討UFH跼部給藥榦預肺內凝血病的閤適劑量.方法 29隻雄性Wistar大鼠經尾靜脈註射大腸桿菌脂多糖(LPS)複製ALI模型,按隨機數字錶法分為對照組(5隻)和UFH組(24隻).UFH組于製模後2h分彆給予6、12、18 U/g的UFH 10 ml霧化吸入1次實施榦預,而對照組則僅用生理鹽水進行霧化吸入.LPS註射後6h處死大鼠,進行肺泡灌洗,收集支氣管肺泡灌洗液(BALF).採用酶聯免疫吸附試驗( ELISA)檢測凝血酶-抗凝血酶複閤物(TATc)、腫瘤壞死因子-α(TNF-α)水平；計算肺組織濕/榦重(W/D)比值,併進行肺損傷病理評分.結果 UFH 6 U/g和12 U/g組BALF中TATc(μg/L)、TNF-α(ng/L)以及肺組織W/D比值、病理評分(分)均明顯低于對照組(TATc:0.959±0.681、1.165±0.854比2.141±0.791,TNF-α:4.449±5.054、9.096±4.099比18.184±3.869,W/D比值:7.018±1.137、7.367±0.349比8.472±0.614,病理評分:16.0±1.0、16.5±1.5比19.6±0.4,P＜0.05或P＜0.01).UFH不同劑量組間BALF中TATc水平和病理評分無差異；UFH 18 U/g組BALF中TNF-α明顯高于UFH 6 U/g組(15.503±8.753比4.449±5.054,P＜0.01)；UFH18 U/g組肺組織W/D比值明顯高于UFH 6 U/g組(8.850±1.157比7.018±1.137,P＜0.05)和12 U/g組(8.850±1.157比7.367±0.349,P＜0.05).結論 霧化吸入不超過12 U/g劑量的UFH治療ALI時,能夠抑製肺泡跼部高凝狀態,減輕早期炎癥反應和肺組織損傷.
목적 통과비교무화흡입불동제량보통간소(UFH)대내독소치급성폐손상(ALI)대서폐부응혈、염증화폐손상조직학적효응,탐토UFH국부급약간예폐내응혈병적합괄제량.방법 29지웅성Wistar대서경미정맥주사대장간균지다당(LPS)복제ALI모형,안수궤수자표법분위대조조(5지)화UFH조(24지).UFH조우제모후2h분별급여6、12、18 U/g적UFH 10 ml무화흡입1차실시간예,이대조조칙부용생리염수진행무화흡입.LPS주사후6h처사대서,진행폐포관세,수집지기관폐포관세액(BALF).채용매련면역흡부시험( ELISA)검측응혈매-항응혈매복합물(TATc)、종류배사인자-α(TNF-α)수평；계산폐조직습/간중(W/D)비치,병진행폐손상병리평분.결과 UFH 6 U/g화12 U/g조BALF중TATc(μg/L)、TNF-α(ng/L)이급폐조직W/D비치、병리평분(분)균명현저우대조조(TATc:0.959±0.681、1.165±0.854비2.141±0.791,TNF-α:4.449±5.054、9.096±4.099비18.184±3.869,W/D비치:7.018±1.137、7.367±0.349비8.472±0.614,병리평분:16.0±1.0、16.5±1.5비19.6±0.4,P＜0.05혹P＜0.01).UFH불동제량조간BALF중TATc수평화병리평분무차이；UFH 18 U/g조BALF중TNF-α명현고우UFH 6 U/g조(15.503±8.753비4.449±5.054,P＜0.01)；UFH18 U/g조폐조직W/D비치명현고우UFH 6 U/g조(8.850±1.157비7.018±1.137,P＜0.05)화12 U/g조(8.850±1.157비7.367±0.349,P＜0.05).결론 무화흡입불초과12 U/g제량적UFH치료ALI시,능구억제폐포국부고응상태,감경조기염증반응화폐조직손상.
Objective To observe the effects of three dosages of nebulized unfractioned heparin (UFH) on alveolar coagulation,inflammation and lung histology in endotoxin-induced acute lung injury rat model,and investigate the appropriated dose of local UFH in managing intrapulmonary coagulopathy.Methods Twenty-nine male Wistar rats were divided into control (n=5) and UFH group (n=24) in table of random number,which were duplicated to be endotoxin-induced ALI rat model with lipopolysaccharide (LPS) injecting by intravenous route.The UFH group was divided into three subgroups,which were administered once with 6,12 and 18 U/g aerosolized UFH in 10 ml at 2 hours after challenge,respectively,while the control group was simply nebulized with normal saline.All rats were sacrificed at 6 hours after intravenous administration of LPS,bronchoalveolar lavage was performed,and the fluid was collected.Enzyme-linked immune sorbent assay (ELISA) was used to measure the level of thrombin-antithrombin complex (TATc),tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF),and lung wet/dry (W/D) weight ratio,histology score were recorded.Results At 6 hours after LPS-induced lung injury,the levels of TATc (μg/L) and TNF-α (ng/L),lung W/D weight ratio and histology score in 6 U/g and 12 U/g group were all lower than those of control group significantly (TATc:0.959 ± 0.681,1.165 ± 0.854 vs.2.141 ± 0.791,TNF-α:4.449 ± 5.054,9.096 ±4.099 vs.18.184 ± 3.869,W/D weight ratio:7.018 ± 1.137,7.367 ± 0.349 vs.8.472 ± 0.614,histology score:16.0 ±1.0,16.5 ± 1.5 vs.19.6 ± 0.4,P＜0.05 or P＜0.01 ).There was no significant difference in the comparisons between the subgroups of UFH in TATc level in BALF and lung histology score.For the TNF-α level in BALF,18 U/g group evidently exceeded that of 6 U/g group ( 15.503 ± 8.753 vs.4.449 ± 5.054,P＜0.01 ),and lung W/D weight ratio in 18 U/g group was also significantly higher comparing to 6 U/g (8.850 ± 1.157 vs.7.018 ± 1.137,P＜0.05 ) and 12 U/g group ( 8.850 ± 1.157 vs.7.367 ± 0.349,P＜0.05 ).Conclusion It was appropriate for the dose of nebulized UFH to be administered no more than 12 U/g in ALI treatment,which was enough to inhibit alveolar coagulant cascade,decrease early inflammatory response and alleviate lung tissue injury.
