中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2011年
4期
239-242
,共4页
汪宗昱%杨拔贤%朱曦%吴胜楠
汪宗昱%楊拔賢%硃晞%吳勝楠
왕종욱%양발현%주희%오성남
普通肝素%内毒素%肺损伤,急性%凝血%纤溶%炎症
普通肝素%內毒素%肺損傷,急性%凝血%纖溶%炎癥
보통간소%내독소%폐손상,급성%응혈%섬용%염증
Unfractioned heparin%Endotoxin%Acute lung injury%Coagulation%Firinolysis%Inflammation
目的 观察内毒素诱导急性肺损伤(ALI)大鼠雾化吸入普通肝素(UFH)后的肺部局部效应,探讨其对肺泡内凝血、纤溶和炎症反应的作用.方法 87只雄性Wistar大鼠按随机数字表法分为假损伤组、模型组、肝素治疗组(HT组)和肝素预防组(HP组).静脉注射(静注)内毒素脂多糖(LPS)制备ALI模型.HP组和HT组分别于注射LPS前后给予UFH雾化吸入,模型组和假损伤组则雾化吸入生理盐水.各组分别于静注LPS后6、12和24 h处死大鼠进行肺泡灌洗,采用酶联免疫吸附法测定支气管肺泡灌洗液(BALF)中凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物(t-PA)、尿激酶型纤溶酶原激活物(u-PA)、纤溶酶原激活物抑制剂-1(PAI-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平.结果 损伤后6 h,模型组BALF中TAT浓度(μg/L:3.346±0.585)最高,其次是HT组(2.764±0.100),HP组(2.564±0.216)最低(均P＜0.05);HP组t-PA(μg/L:3.037±0.524)最高,HT组(2.494±0.191)其次,模型组(1.716±0.125)最低(均P＜0.05);HP组u-PA(μg/L)高于模型组(0.411±0.118比0.303±0.049,P＜0.05);HP组PAI-1(μg/L)明显低于HT组和模型组(2.296±0.246比2.597±0.425、2.834±0.198,均P＜0.05),直至12 h时HP组仍低于HT组(1.273±0.441比1.817±0.252,P＜0.05);HT组和HP组TNF-α(ng/L)显著低于模型组(68.154±3.915、36.990±6.539比77.001±4.485),且HP组低于HT组(均P＜0.05),至12 h HP组(15.287±4.754)仍最低,与HT组和模型组(26.756±5.336、23.674±4.398)比较差异有统计学意义(均P＜0.05).模型组、HT组和HP组各时间点IL-6水平均无明显差异.结论 内毒素性ALI大鼠雾化吸入UFH后起到了抑制局部凝血、减弱纤溶抑制、促进纤溶、降低炎症反应的作用,预防性吸人UFH比治疗性吸入效果更显著,最佳效应时间在注射后6 h.
目的 觀察內毒素誘導急性肺損傷(ALI)大鼠霧化吸入普通肝素(UFH)後的肺部跼部效應,探討其對肺泡內凝血、纖溶和炎癥反應的作用.方法 87隻雄性Wistar大鼠按隨機數字錶法分為假損傷組、模型組、肝素治療組(HT組)和肝素預防組(HP組).靜脈註射(靜註)內毒素脂多糖(LPS)製備ALI模型.HP組和HT組分彆于註射LPS前後給予UFH霧化吸入,模型組和假損傷組則霧化吸入生理鹽水.各組分彆于靜註LPS後6、12和24 h處死大鼠進行肺泡灌洗,採用酶聯免疫吸附法測定支氣管肺泡灌洗液(BALF)中凝血酶-抗凝血酶複閤物(TAT)、組織型纖溶酶原激活物(t-PA)、尿激酶型纖溶酶原激活物(u-PA)、纖溶酶原激活物抑製劑-1(PAI-1)、腫瘤壞死因子-α(TNF-α)、白細胞介素-6(IL-6)水平.結果 損傷後6 h,模型組BALF中TAT濃度(μg/L:3.346±0.585)最高,其次是HT組(2.764±0.100),HP組(2.564±0.216)最低(均P＜0.05);HP組t-PA(μg/L:3.037±0.524)最高,HT組(2.494±0.191)其次,模型組(1.716±0.125)最低(均P＜0.05);HP組u-PA(μg/L)高于模型組(0.411±0.118比0.303±0.049,P＜0.05);HP組PAI-1(μg/L)明顯低于HT組和模型組(2.296±0.246比2.597±0.425、2.834±0.198,均P＜0.05),直至12 h時HP組仍低于HT組(1.273±0.441比1.817±0.252,P＜0.05);HT組和HP組TNF-α(ng/L)顯著低于模型組(68.154±3.915、36.990±6.539比77.001±4.485),且HP組低于HT組(均P＜0.05),至12 h HP組(15.287±4.754)仍最低,與HT組和模型組(26.756±5.336、23.674±4.398)比較差異有統計學意義(均P＜0.05).模型組、HT組和HP組各時間點IL-6水平均無明顯差異.結論 內毒素性ALI大鼠霧化吸入UFH後起到瞭抑製跼部凝血、減弱纖溶抑製、促進纖溶、降低炎癥反應的作用,預防性吸人UFH比治療性吸入效果更顯著,最佳效應時間在註射後6 h.
목적 관찰내독소유도급성폐손상(ALI)대서무화흡입보통간소(UFH)후적폐부국부효응,탐토기대폐포내응혈、섬용화염증반응적작용.방법 87지웅성Wistar대서안수궤수자표법분위가손상조、모형조、간소치료조(HT조)화간소예방조(HP조).정맥주사(정주)내독소지다당(LPS)제비ALI모형.HP조화HT조분별우주사LPS전후급여UFH무화흡입,모형조화가손상조칙무화흡입생리염수.각조분별우정주LPS후6、12화24 h처사대서진행폐포관세,채용매련면역흡부법측정지기관폐포관세액(BALF)중응혈매-항응혈매복합물(TAT)、조직형섬용매원격활물(t-PA)、뇨격매형섬용매원격활물(u-PA)、섬용매원격활물억제제-1(PAI-1)、종류배사인자-α(TNF-α)、백세포개소-6(IL-6)수평.결과 손상후6 h,모형조BALF중TAT농도(μg/L:3.346±0.585)최고,기차시HT조(2.764±0.100),HP조(2.564±0.216)최저(균P＜0.05);HP조t-PA(μg/L:3.037±0.524)최고,HT조(2.494±0.191)기차,모형조(1.716±0.125)최저(균P＜0.05);HP조u-PA(μg/L)고우모형조(0.411±0.118비0.303±0.049,P＜0.05);HP조PAI-1(μg/L)명현저우HT조화모형조(2.296±0.246비2.597±0.425、2.834±0.198,균P＜0.05),직지12 h시HP조잉저우HT조(1.273±0.441비1.817±0.252,P＜0.05);HT조화HP조TNF-α(ng/L)현저저우모형조(68.154±3.915、36.990±6.539비77.001±4.485),차HP조저우HT조(균P＜0.05),지12 h HP조(15.287±4.754)잉최저,여HT조화모형조(26.756±5.336、23.674±4.398)비교차이유통계학의의(균P＜0.05).모형조、HT조화HP조각시간점IL-6수평균무명현차이.결론 내독소성ALI대서무화흡입UFH후기도료억제국부응혈、감약섬용억제、촉진섬용、강저염증반응적작용,예방성흡인UFH비치료성흡입효과경현저,최가효응시간재주사후6 h.
Objective To observe the local changes in alveoli in intravenous endotoxin-induced acute lung injury (ALI) rat model after inhalation of aerosolized unfractioned heparin(UFH), and to observe its effects on coagulability, fibrinolysis and inflammatory response. Methods Eighty-seven male Wistar rats were divided into groups according to table of random number: sham, model, heparin therapy (HT) and heparin prophylaxis(HP). Endotoxin-induced ALI model was reproduced by intravenous administration of lipopolysaccharide (LPS). Rats in Hp and HT groups received aerosolized UFH before and after injection with LPS respectively, while rats in both sham and model groups inhaled aerosolized normal saline. Rats in each group were respectively sacrificed at 6, 12 and 24 hours after intravenous administration of LPS, and bronchoalveolar lavage fluid (BALF) was collected. Enzyme-linked immunosorbent assay was used to measure the level of thrombin-antithrombin (TAT), tissue-type plasminogen activator (t-PA),urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor- (TNF-α), interleukin-6 (IL-6) in BALF. Results At.6 hours after injury, the level of TAT (μg/L) in model group (3.346±0. 585) was highest, that in HT group (22. 764±0. 100) was higher, and that in HP group (2. 564±0. 2216) was lowest in BALF (all P＜0. 05). The t-PA(μg/L) concentration in HP group (3.037±0. 5224) was highest, that in HT group (22. 494±0. 191) was higher, and that in model group (1. 716±0. 1225) was lowest (all P＜0. 05). Compared with model group, u-PA (μg/L) level in HP group dramatically enhanced (0. 411±0. 118 vs. 0. 303±0. 049, P＜0. 05). The concentration of PAI-1 (μg/L) in HP group was significantly lower than that of HT and model groups (22. 2296 ± 0. 2246 vs. 22.597±0. 4225,2.834±0.198, both P＜0. 05). In HP group, it was still lower than that in HT group at 12 hours (1.2273±0. 441 vs. 1. 817±0. 252, P＜0. 05). TNF-α(ng/L) levels in HT and HP groups were markedly lower compared with model group (68. 154±3. 915, 36. 990±6. 539 vs. 77. 001±4. 485) at 6 hours, and the level in HP group was lower than that in HT group (all P＜0. 05). TNF-α concentration in HP group was still the lowest at 122 hours (15.2287±4. 754), and there was significant difference compared with HT and model groups (26. 756±5. 336, 23. 674±4. 398, both P＜0. 05). The levels of IL-6 were not distinctively different among model, HT and HP groups at various time-points. Conclusion It was proved that inhalation of aerosolized UFH resulted in lowering local coagulability, alleviating fibrinolytic depression, improving fibrinolysis, and attenuating inflammation in endotoxin-induced ALI rat model. More prominent results will be obtained when it was use as a prophylactic measure. The optimal time of usage is 6 hours after endotoxin injection.
