CAJ | 학술논문

目的：创伤失血性休克患者常常合并肝损伤，白细胞介素1β（ interleukin-1β， IL-1β）是参与该过程的重要炎性因子。文中通过制备创伤失血性休克模型，观察肝组织损伤相关指标，研究IL-1β通路重要信号分子髓样分化因子88（ mye-loid differentiation primary response gene 88， Myd88）的Toll IL-1受体同源区域（Toll IL-1 recptor homology， TIR）/BB环状拟似物氢化肉桂基-L-缬氨酰吡咯烷（ hydrocinnamoyl-L-valyl pyrrolidine ， AS-1）对创伤失血性休克大鼠再灌注后肝损伤的影响。方法32只雄性SD大鼠随机分为创伤失血性休克复苏组（模型组）、创伤失血性休克联合AS-1复苏组（ AS-1组）、创伤失血性休克联合溶剂复苏组（溶剂组）、对照组。模型组、AS-1组、溶剂组钳夹胫骨致骨折，股动脉放血将平均动脉压（ mean arterial pressure， MAP）降至30mmHg（1mmHg＝0．133kPa），维持于30～40mmHg 1h，以血液及林格溶液按比例于30min内匀速回输；AS-1组复苏前予AS-1（160 mg/kg）；溶剂组复苏前予等比例溶剂；对照组无处理。模型组、AS-1组、溶剂组大鼠复苏后3 h，对照组保留插管2．5 h后隔3 h，测血清天冬氨酸氨基转移酶（aspartate transaminase， AST）、丙氨酸氨基转移酶（alanine amin-otransferase， ALT）活性及IL-1β、肿瘤坏死因子α（tumor necrosis factor-α， TNF-α）的含量，测肝左叶髓过氧化物酶（myeloperoxi-dase， MPO）活性并光镜下观察其病理改变。结果与对照组比，模型组、AS-1组、溶剂组大鼠血清ALT、AST活性，IL-1β、TNF-α含量，肝组织MPO活性均明显升高（P＜0．05），病理损伤明显；与模型组、溶剂组比，AS-1组大鼠上述指标均降低（P＜0．05），而模型组、溶剂组组间差异无统计学意义（P＞0．05）。结论 TIR/BB环状拟似物AS-1可通过减少IL-1β、TNF-α含量，减少肝组织内中性粒细胞聚集来减轻创伤失血性休克大鼠再灌注后肝损伤。目的：創傷失血性休剋患者常常閤併肝損傷，白細胞介素1β（ interleukin-1β， IL-1β）是參與該過程的重要炎性因子。文中通過製備創傷失血性休剋模型，觀察肝組織損傷相關指標，研究IL-1β通路重要信號分子髓樣分化因子88（ mye-loid differentiation primary response gene 88， Myd88）的Toll IL-1受體同源區域（Toll IL-1 recptor homology， TIR）/BB環狀擬似物氫化肉桂基-L-纈氨酰吡咯烷（ hydrocinnamoyl-L-valyl pyrrolidine ， AS-1）對創傷失血性休剋大鼠再灌註後肝損傷的影響。方法32隻雄性SD大鼠隨機分為創傷失血性休剋複囌組（模型組）、創傷失血性休剋聯閤AS-1複囌組（ AS-1組）、創傷失血性休剋聯閤溶劑複囌組（溶劑組）、對照組。模型組、AS-1組、溶劑組鉗夾脛骨緻骨摺，股動脈放血將平均動脈壓（ mean arterial pressure， MAP）降至30mmHg（1mmHg＝0．133kPa），維持于30～40mmHg 1h，以血液及林格溶液按比例于30min內勻速迴輸；AS-1組複囌前予AS-1（160 mg/kg）；溶劑組複囌前予等比例溶劑；對照組無處理。模型組、AS-1組、溶劑組大鼠複囌後3 h，對照組保留插管2．5 h後隔3 h，測血清天鼕氨痠氨基轉移酶（aspartate transaminase， AST）、丙氨痠氨基轉移酶（alanine amin-otransferase， ALT）活性及IL-1β、腫瘤壞死因子α（tumor necrosis factor-α， TNF-α）的含量，測肝左葉髓過氧化物酶（myeloperoxi-dase， MPO）活性併光鏡下觀察其病理改變。結果與對照組比，模型組、AS-1組、溶劑組大鼠血清ALT、AST活性，IL-1β、TNF-α含量，肝組織MPO活性均明顯升高（P＜0．05），病理損傷明顯；與模型組、溶劑組比，AS-1組大鼠上述指標均降低（P＜0．05），而模型組、溶劑組組間差異無統計學意義（P＞0．05）。結論 TIR/BB環狀擬似物AS-1可通過減少IL-1β、TNF-α含量，減少肝組織內中性粒細胞聚集來減輕創傷失血性休剋大鼠再灌註後肝損傷。
목적：창상실혈성휴극환자상상합병간손상，백세포개소1β（ interleukin-1β， IL-1β）시삼여해과정적중요염성인자。문중통과제비창상실혈성휴극모형，관찰간조직손상상관지표，연구IL-1β통로중요신호분자수양분화인자88（ mye-loid differentiation primary response gene 88， Myd88）적Toll IL-1수체동원구역（Toll IL-1 recptor homology， TIR）/BB배상의사물경화육계기-L-힐안선필각완（ hydrocinnamoyl-L-valyl pyrrolidine ， AS-1）대창상실혈성휴극대서재관주후간손상적영향。방법32지웅성SD대서수궤분위창상실혈성휴극복소조（모형조）、창상실혈성휴극연합AS-1복소조（ AS-1조）、창상실혈성휴극연합용제복소조（용제조）、대조조。모형조、AS-1조、용제조겸협경골치골절，고동맥방혈장평균동맥압（ mean arterial pressure， MAP）강지30mmHg（1mmHg＝0．133kPa），유지우30～40mmHg 1h，이혈액급림격용액안비례우30min내균속회수；AS-1조복소전여AS-1（160 mg/kg）；용제조복소전여등비례용제；대조조무처리。모형조、AS-1조、용제조대서복소후3 h，대조조보류삽관2．5 h후격3 h，측혈청천동안산안기전이매（aspartate transaminase， AST）、병안산안기전이매（alanine amin-otransferase， ALT）활성급IL-1β、종류배사인자α（tumor necrosis factor-α， TNF-α）적함량，측간좌협수과양화물매（myeloperoxi-dase， MPO）활성병광경하관찰기병리개변。결과여대조조비，모형조、AS-1조、용제조대서혈청ALT、AST활성，IL-1β、TNF-α함량，간조직MPO활성균명현승고（P＜0．05），병리손상명현；여모형조、용제조비，AS-1조대서상술지표균강저（P＜0．05），이모형조、용제조조간차이무통계학의의（P＞0．05）。결론 TIR/BB배상의사물AS-1가통과감소IL-1β、TNF-α함량，감소간조직내중성립세포취집래감경창상실혈성휴극대서재관주후간손상。
Objective Traumatic hemorrhagic shock ( THS) is frequently complicated by liver injury , and IL-1βis one of the important inflammatory factors involved in this process .We ob-served changes of liver injury-related indexes in the rat model of THS and investigated the effects of AS-1, the mimic of the TIR/BB loop of Myd88, an important molecule of the IL-1βsignal pathway, on liver injury triggered by ischemia/reperfusion following THS and resuscita-tion ( THSR) in rats. Methods Thirty-two healthy male SD rats <br> were randomly divided into groups A (THSR), B ( THSR+AS-1), C (THSR+dissolution medium), and D (control).For those of the first three groups , fracture was induced in the left tibia , the mean arterial pressure reduced to 30 mmHg by bloodletting from the femoral artery and maintained at 30-40 mmHg for an hour , and then the rats resuscitated by infusion of blood and Ringer′s solution in proportion at a uniform speed in 30 min.Before resuscitation, the rats in group B were treated with AS-1 (160 mg/kg), group C with dissolution medium, and group D left untreated .At 3 hours after resuscitation in groups A , B and C, and at 3 hours after 2.5h-our in-tubation in group D , we detected the activity of ALT , the levels of AST , IL-1βand TNF-α, and the activity of MPO in the left liver , and observed pathological changes in the liver by light microscopy . Results Compared with group D, groups A, B and C showed ev-ident liver injury and significant increases in the activity of ALT (87.55 ±6.8 vs 206.13 ±23.67, 110.45 ±18.20 and 210.73 ± 28.43), AST (327.03 ±36.23 vs 621.00 ±40.61, 409.13 ±63.53 and 600.25 ±44.05), the levels of IL-1β(327.03 ±36.23 vs 621.00 ±40.61, 409.13 ±63.53 and 600.25 ±44.05) and TNF-α(93.51 ±9.86 vs 214.13 ±21.24, 145.25 ±12.42 and 206.50 ± 36.97), and the activity of MPO (0.90 ±0.21 vs 1.72 ±0.12, 1.20 ±0.11 and 1.67 ±0.14) (all P<0.05).The above indexes were remarkably lower in group B than in A and C, (all P<0.05), but with no significant differences between the latter two groups (P>0.05).Conclusion TIR/BB-loop mimetic AS-1 can attenuate ischemia/reperfusion-induced liver injury after THSR in rats by decrea -sing the levels of IL1-βand TNF-αin the serum.