中华危重病急救医学
中華危重病急救醫學
중화위중병급구의학
Chinese Critical Care Medicine
2015年
2期
92-96
,共5页
陆晓华%李伟%王国光%汪全海%姜玉新%高家林%赵雪%徐蕾
陸曉華%李偉%王國光%汪全海%薑玉新%高傢林%趙雪%徐蕾
륙효화%리위%왕국광%왕전해%강옥신%고가림%조설%서뢰
硫化氢%弥散性血管内凝血%肠系膜微循环
硫化氫%瀰散性血管內凝血%腸繫膜微循環
류화경%미산성혈관내응혈%장계막미순배
Hydrogen sulfide%Disseminated intravascular coagulation%Microcirculation in the mesentery
目的：探讨外源性硫化氢（H2S）对组织因子诱导的弥散性血管内凝血（DIC）家兔的保护作用及其机制。方法将32只健康家兔按照随机数字表法分为正常对照组、硫氢化钠（NaHS）对照组、DIC模型组、NaHS预处理组，每组8只。制模前10 min，NaHS对照组和NaHS预处理组经耳缘静脉注射NaHS溶液3.4 mg/kg（加生理盐水至5 mL混匀溶解），正常对照组和DIC模型组注射等量生理盐水；10 min注射完毕后，DIC模型组及NaHS预处理组经耳缘静脉注射冻干兔脑组织因子悬液2 mL/kg（生理盐水稀释至30 mL，以1 mL/min×5 min、2 mL/min×5 min、3 mL/min×5 min的速度注入），正常对照组和NaHS对照组注射等量生理盐水。各组分别于注射组织因子前10 min及注射后3、5、8、10、13、15、45、85、135 min颈总动脉采血3 mL，检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）、纤维蛋白原降解产物（FDP）及血小板计数（PLT）；同时观察肠系膜微循环。结果与正常对照组比较，DIC模型组注射组织因子5 min时PT、APTT缩短，其变化率明显增大〔PT：-8.3（-11.7～-5.3）%比1.3（-2.5～3.8）%，P＜0.01；APTT：-19.1（-30.4～-9.4）%比-2.6（-6.2～3.0）%，P＜0.05〕；15 min后PT、 APTT延长，其变化率明显增大〔PT：31.0（25.0～36.9）%比-1.3（-6.3～5.0）%，APTT：61.3（50.0～72.9）%比0.0（-10.0～10.0）%，均P＜0.01〕；注射组织因子后TT逐渐缩短，FIB、PLT逐渐降低，在15 min时其变化率明显增大〔TT：-9.5（-12.0～-6.2）%比-2.0（-4.0～0.7）%，FIB：-4.3（-9.9～-2.2）%比-1.0（-5.8～4.3）%，PLT：-90.0（-93.4～-86.5）%比-1.0（-3.9～2.6）%，均P＜0.01〕；注射组织因子后FDP测试板圆圈内均有乳胶颗粒凝集，且在3～15 min乳胶颗粒凝集逐渐增强，之后逐渐减弱；肠系膜毛细血管血流速于10 min内明显变慢，之后逐渐变快并伴有明显出血。NaHS预处理组注射组织因子5 min时PT、APTT缩短，其变化率较DIC模型组明显减小〔PT：-6.3（-8.6～0.0）%比-8.3（-11.7～-5.3）%，APTT：-13.6（-24.2～-2.3）%比-19.1（-30.4～-9.4）%，均P＜0.05〕；15 min后PT、 APTT延长，但其变化率较DIC模型组明显减小〔PT：10.1（3.8～15.2）%比31.0（25.0～36.9）%， P＜0.01；APTT：27.8（-15.8～39.7）%比61.3（50.0～72.9）%，P＜0.05〕；15 min时TT缩短，FIB、PLT降低，但其变化率较DIC模型组明显减小〔TT：-4.5（-7.8～-1.3）%比-9.5（-12.0～-6.2）%，P＜0.01；FIB：-3.3（-8.0～1.9）%比-4.3（-9.9～-2.2）%，P＜0.05；PLT：-58.8（-53.0～64.0）%比-90.0（-93.4～-86.5）%，P＜0.01〕；各时间点乳胶颗粒凝集较DIC模型组明显减弱；肠系膜毛细血管血流速10 min内逐渐变慢，但较DIC模型组快，之后变快，且出血明显减少。结论 H2S对实验性DIC有一定的防治作用，其作用机制可能与其抑制组织因子引起的凝血系统激活及血小板聚集有关。
目的：探討外源性硫化氫（H2S）對組織因子誘導的瀰散性血管內凝血（DIC）傢兔的保護作用及其機製。方法將32隻健康傢兔按照隨機數字錶法分為正常對照組、硫氫化鈉（NaHS）對照組、DIC模型組、NaHS預處理組，每組8隻。製模前10 min，NaHS對照組和NaHS預處理組經耳緣靜脈註射NaHS溶液3.4 mg/kg（加生理鹽水至5 mL混勻溶解），正常對照組和DIC模型組註射等量生理鹽水；10 min註射完畢後，DIC模型組及NaHS預處理組經耳緣靜脈註射凍榦兔腦組織因子懸液2 mL/kg（生理鹽水稀釋至30 mL，以1 mL/min×5 min、2 mL/min×5 min、3 mL/min×5 min的速度註入），正常對照組和NaHS對照組註射等量生理鹽水。各組分彆于註射組織因子前10 min及註射後3、5、8、10、13、15、45、85、135 min頸總動脈採血3 mL，檢測凝血酶原時間（PT）、活化部分凝血活酶時間（APTT）、凝血酶時間（TT）、纖維蛋白原（FIB）、纖維蛋白原降解產物（FDP）及血小闆計數（PLT）；同時觀察腸繫膜微循環。結果與正常對照組比較，DIC模型組註射組織因子5 min時PT、APTT縮短，其變化率明顯增大〔PT：-8.3（-11.7～-5.3）%比1.3（-2.5～3.8）%，P＜0.01；APTT：-19.1（-30.4～-9.4）%比-2.6（-6.2～3.0）%，P＜0.05〕；15 min後PT、 APTT延長，其變化率明顯增大〔PT：31.0（25.0～36.9）%比-1.3（-6.3～5.0）%，APTT：61.3（50.0～72.9）%比0.0（-10.0～10.0）%，均P＜0.01〕；註射組織因子後TT逐漸縮短，FIB、PLT逐漸降低，在15 min時其變化率明顯增大〔TT：-9.5（-12.0～-6.2）%比-2.0（-4.0～0.7）%，FIB：-4.3（-9.9～-2.2）%比-1.0（-5.8～4.3）%，PLT：-90.0（-93.4～-86.5）%比-1.0（-3.9～2.6）%，均P＜0.01〕；註射組織因子後FDP測試闆圓圈內均有乳膠顆粒凝集，且在3～15 min乳膠顆粒凝集逐漸增彊，之後逐漸減弱；腸繫膜毛細血管血流速于10 min內明顯變慢，之後逐漸變快併伴有明顯齣血。NaHS預處理組註射組織因子5 min時PT、APTT縮短，其變化率較DIC模型組明顯減小〔PT：-6.3（-8.6～0.0）%比-8.3（-11.7～-5.3）%，APTT：-13.6（-24.2～-2.3）%比-19.1（-30.4～-9.4）%，均P＜0.05〕；15 min後PT、 APTT延長，但其變化率較DIC模型組明顯減小〔PT：10.1（3.8～15.2）%比31.0（25.0～36.9）%， P＜0.01；APTT：27.8（-15.8～39.7）%比61.3（50.0～72.9）%，P＜0.05〕；15 min時TT縮短，FIB、PLT降低，但其變化率較DIC模型組明顯減小〔TT：-4.5（-7.8～-1.3）%比-9.5（-12.0～-6.2）%，P＜0.01；FIB：-3.3（-8.0～1.9）%比-4.3（-9.9～-2.2）%，P＜0.05；PLT：-58.8（-53.0～64.0）%比-90.0（-93.4～-86.5）%，P＜0.01〕；各時間點乳膠顆粒凝集較DIC模型組明顯減弱；腸繫膜毛細血管血流速10 min內逐漸變慢，但較DIC模型組快，之後變快，且齣血明顯減少。結論 H2S對實驗性DIC有一定的防治作用，其作用機製可能與其抑製組織因子引起的凝血繫統激活及血小闆聚集有關。
목적：탐토외원성류화경（H2S）대조직인자유도적미산성혈관내응혈（DIC）가토적보호작용급기궤제。방법장32지건강가토안조수궤수자표법분위정상대조조、류경화납（NaHS）대조조、DIC모형조、NaHS예처리조，매조8지。제모전10 min，NaHS대조조화NaHS예처리조경이연정맥주사NaHS용액3.4 mg/kg（가생리염수지5 mL혼균용해），정상대조조화DIC모형조주사등량생리염수；10 min주사완필후，DIC모형조급NaHS예처리조경이연정맥주사동간토뇌조직인자현액2 mL/kg（생리염수희석지30 mL，이1 mL/min×5 min、2 mL/min×5 min、3 mL/min×5 min적속도주입），정상대조조화NaHS대조조주사등량생리염수。각조분별우주사조직인자전10 min급주사후3、5、8、10、13、15、45、85、135 min경총동맥채혈3 mL，검측응혈매원시간（PT）、활화부분응혈활매시간（APTT）、응혈매시간（TT）、섬유단백원（FIB）、섬유단백원강해산물（FDP）급혈소판계수（PLT）；동시관찰장계막미순배。결과여정상대조조비교，DIC모형조주사조직인자5 min시PT、APTT축단，기변화솔명현증대〔PT：-8.3（-11.7～-5.3）%비1.3（-2.5～3.8）%，P＜0.01；APTT：-19.1（-30.4～-9.4）%비-2.6（-6.2～3.0）%，P＜0.05〕；15 min후PT、 APTT연장，기변화솔명현증대〔PT：31.0（25.0～36.9）%비-1.3（-6.3～5.0）%，APTT：61.3（50.0～72.9）%비0.0（-10.0～10.0）%，균P＜0.01〕；주사조직인자후TT축점축단，FIB、PLT축점강저，재15 min시기변화솔명현증대〔TT：-9.5（-12.0～-6.2）%비-2.0（-4.0～0.7）%，FIB：-4.3（-9.9～-2.2）%비-1.0（-5.8～4.3）%，PLT：-90.0（-93.4～-86.5）%비-1.0（-3.9～2.6）%，균P＜0.01〕；주사조직인자후FDP측시판원권내균유유효과립응집，차재3～15 min유효과립응집축점증강，지후축점감약；장계막모세혈관혈류속우10 min내명현변만，지후축점변쾌병반유명현출혈。NaHS예처리조주사조직인자5 min시PT、APTT축단，기변화솔교DIC모형조명현감소〔PT：-6.3（-8.6～0.0）%비-8.3（-11.7～-5.3）%，APTT：-13.6（-24.2～-2.3）%비-19.1（-30.4～-9.4）%，균P＜0.05〕；15 min후PT、 APTT연장，단기변화솔교DIC모형조명현감소〔PT：10.1（3.8～15.2）%비31.0（25.0～36.9）%， P＜0.01；APTT：27.8（-15.8～39.7）%비61.3（50.0～72.9）%，P＜0.05〕；15 min시TT축단，FIB、PLT강저，단기변화솔교DIC모형조명현감소〔TT：-4.5（-7.8～-1.3）%비-9.5（-12.0～-6.2）%，P＜0.01；FIB：-3.3（-8.0～1.9）%비-4.3（-9.9～-2.2）%，P＜0.05；PLT：-58.8（-53.0～64.0）%비-90.0（-93.4～-86.5）%，P＜0.01〕；각시간점유효과립응집교DIC모형조명현감약；장계막모세혈관혈류속10 min내축점변만，단교DIC모형조쾌，지후변쾌，차출혈명현감소。결론 H2S대실험성DIC유일정적방치작용，기작용궤제가능여기억제조직인자인기적응혈계통격활급혈소판취집유관。
ObjectiveTo investigate the protective effect of hydrogen sulfide (H2S) on tissue factor-induced disseminated intravascular coagulation (DIC) in rabbits and its mechanism.Methods Thirty-two healthy rabbits were randomly divided into four groups: normal control group, NaHS control group, DIC model group, NaHS pretreatment group (each,n = 8). Ten minutes before model reproduction, rabbits in NaHS control and pretreatment groups were given 3.4 mg/kg NaHS (dissolved in normal saline to 5 mL) via ear vein, while rabbits in normal control and DIC model groups were given an equivalent volume of normal saline. Ten minutes later, rabbits in DIC model and NaHS pretreatment groups were intravenously given tissue factor (TF) 2 mL/kg (dissolved in normal saline to 30 mL, at the speed of 1 mL/min for 5 minutes, 2 mL/min for 5 minutes, and 3 mL/min for 5 minutes), and rabbits in normal control and NaHS control groups were given normal saline. 3 mL of blood was collected 10 minutes before TF injection, and 3, 5, 8, 10, 13, 15, 45, 85, 135 minutes after TF injection for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen content (FIB), fibrin degradation products (FDP), and platelet count ( PLT ). Microcirculation in the mesentery was also observed under microscope.Results Compared with normal control group, PT and APTT became shorter at 5 minutes after TF injection, and the rate of their change was increased [PT: -8.3 (-11.7 to -5.3)% vs. 1.3 (-2.5 to 3.8)%,P< 0.01; APTT: -19.1 (-30.4 to -9.4)% vs. -2.6 (-6.2 to 3.0)%,P< 0.05]. PT and APTT were prolonged 15 minutes after TF injection, and their changes were more significant [PT: 31.0 (25.0 to 36.9)% vs. -1.3 (-6.3 to 5.0)%, APTT: 61.3 (50.0 to 72.9)% vs. 0.0 (-10.0 to 10.0)%, bothP< 0.01] in DIC model group. TT was gradually reduced after TF injection, FIB and PLT were gradually decreased, and their changes were more obvious at 15 minutes in DIC model group compared with those in normal control group [TT: -9.5 (-12.0 to -6.2)% vs. -2.0 (-4.0 to 0.7)%, FIB: -4.3 (-9.9 to -2.2)% vs. -1.0 (-5.8 to 4.3)%, PLT: -90.0 (-93.4 to -86.5)%vs. -1.0 (-3.9 to 2.6), allP< 0.01]. After TF injection, it appeared latex-like particles in FDP test board, and it was gradually increased within 3-15 minutes, and then it gradually became less marked. The rate of blood flow in mesenteric capillaries was decreased obviously within 10 minutes, and it became faster accompanying with obvious hemorrhage. PT and APTT in NaHS pretreatment group became shortened 5 minutes after TF injection, and their rate of change was significantly decreased compared with that of DIC model group [PT: -6.3 (-8.6 to 0.0)% vs. -8.3 (-11.7 to-5.3)%, APTT: -13.6 (-24.2 to -2.3)% vs. -19.1 (-30.4 to -9.4)%, bothP< 0.05], and prolonged at 15 minutes, and their rate of change was significantly decreased compared with that of DIC model group [PT: 10.1 (3.8 to 15.2)% vs. 31.0 (25.0 to 36.9)%,P< 0.01; APTT: 27.8 (-15.8 to 39.7)% vs. 61.3 (50.0 to 72.9)%,P< 0.05]. TT, FIB, and PLT were reduced at 15 minutes in NaHS pretreatment group, and their rate of change was markedly decreased compared with that of DIC model group [TT: -4.5 (-7.8 to -1.3)% vs. -9.5 (-12.0 to -6.2)%,P< 0.01; FIB: -3.3 (-8.0 to 1.9)%vs. -4.3 ( -9.9 to -2.2 )%,P< 0.05; PLT: -58.8 (-53.0 to 64.0)% vs. -90.0 (-93.4 to -86.5)%,P< 0.01]. The rate of agglutination of latex particles in NaHS pretreatment group was decreased significantly at each time point compared with DIC model group; mesenteric capillary blood flow slowed down gradually within 10 minutes, but it was faster as compared with the DIC model group. It became faster later, but bleeding was obviously less.Conclusion These results show that H2S protects against TF-induced DIC by inhibiting the activity of coagulation system and platelet aggregation.
<br> NaHS (dissolved in normal saline to 5 mL) via ear vein, while rabbits in normal control and DIC model groups were given an equivalent volume of normal saline. Ten minutes later, rabbits in DIC model and NaHS pretreatment groups were intravenously given tissue factor (TF) 2 mL/kg (dissolved in normal saline to 30 mL, at the speed of 1 mL/min for 5 minutes, 2 mL/min for 5 minutes, and 3 mL/min for 5 minutes), and rabbits in normal control and NaHS control groups were given normal saline. 3 mL of blood was collected 10 minutes before TF injection, and 3, 5, 8, 10, 13, 15, 45, 85, 135 minutes after TF injection for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen content (FIB), fibrin degradation products (FDP), and platelet count ( PLT ). Microcirculation in the mesentery was also observed under microscope.Results Compared with normal control group, PT and APTT became shorter at 5 minutes after TF injection, and the rate of their change was increased [PT: -8.3 (-11.7 to -5.3)% vs. 1.3 (-2.5 to 3.8)%,P< 0.01; APTT: -19.1 (-30.4 to -9.4)% vs. -2.6 (-6.2 to 3.0)%,P< 0.05]. PT and APTT were prolonged 15 minutes after TF injection, and their changes were more significant [PT: 31.0 (25.0 to 36.9)% vs. -1.3 (-6.3 to 5.0)%, APTT: 61.3 (50.0 to 72.9)% vs. 0.0 (-10.0 to 10.0)%, bothP< 0.01] in DIC model group. TT was gradually reduced after TF injection, FIB and PLT were gradually decreased, and their changes were more obvious at 15 minutes in DIC model group compared with those in normal control group [TT: -9.5 (-12.0 to -6.2)% vs. -2.0 (-4.0 to 0.7)%, FIB: -4.3 (-9.9 to -2.2)% vs. -1.0 (-5.8 to 4.3)%, PLT: -90.0 (-93.4 to -86.5)%vs. -1.0 (-3.9 to 2.6), allP< 0.01]. After TF injection, it appeared latex-like particles in FDP test board, and it was gradually increased within 3-15 minutes, and then it gradually became less marked. The rate of blood flow in mesenteric capillaries was decreased obviously within 10 minutes, and it became faster accompanying with obvious hemorrhage. PT and APTT in NaHS pretreatment group became shortened 5 minutes after TF injection, and their rate of change was significantly decreased compared with that of DIC model group [PT: -6.3 (-8.6 to 0.0)% vs. -8.3 (-11.7 to-5.3)%, APTT: -13.6 (-24.2 to -2.3)% vs. -19.1 (-30.4 to -9.4)%, bothP< 0.05], and prolonged at 15 minutes, and their rate of change was significantly decreased compared with that of DIC model group [PT: 10.1 (3.8 to 15.2)% vs. 31.0 (25.0 to 36.9)%,P< 0.01; APTT: 27.8 (-15.8 to 39.7)% vs. 61.3 (50.0 to 72.9)%,P< 0.05]. TT, FIB, and PLT were reduced at 15 minutes in NaHS pretreatment group, and their rate of change was markedly decreased compared with that of DIC model group [TT: -4.5 (-7.8 to -1.3)% vs. -9.5 (-12.0 to -6.2)%,P< 0.01; FIB: -3.3 (-8.0 to 1.9)%vs. -4.3 ( -9.9 to -2.2 )%,P< 0.05; PLT: -58.8 (-53.0 to 64.0)% vs. -90.0 (-93.4 to -86.5)%,P< 0.01]. The rate of agglutination of latex particles in NaHS pretreatment group was decreased significantly at each time point compared with DIC model group; mesenteric capillary blood flow slowed down gradually within 10 minutes, but it was faster as compared with the DIC model group. It became faster later, but bleeding was obviously less.Conclusion These results show that H2S protects against TF-induced DIC by inhibiting the activity of coagulation system and platelet aggregation.
