CAJ | 학술논문

目的：研究复方依达拉奉注射液对脓毒症体内及体外模型的影响。方法：将130只SD大鼠随机分为7组：假手术组（Sham）、模型组（Model）、依达拉奉低剂量组（3 mg·kg-1）、依达拉奉高剂量组（6 mg·kg-1）、复方依达拉奉低剂量组（3.75 mg·kg-1）、复方依达拉奉高剂量组（7.5 mg·kg-1）、冰片组（给予2-莰醇1.5 mg·kg-1）；除假手术组10只外，每组均为20只。 Sham组仅开腹不结扎，其余组均采用盲肠结扎穿孔术建立大鼠脓毒症模型。术后30 min、4 h、12 h分别交叉循环尾静脉注射相应的药物，假手术组与模型组给予生理盐水。术后6 h，检测血清肿瘤坏死因子α（TNF-α）、白介素6（IL-6）、谷草转氨酶（AST）、碱性磷酸酶（ALP）和总胆红素（TBIL）水平，并观察动物24 h生存率。采用LPS刺激小鼠RAW 264.7巨噬细胞建立炎症模型，在不同浓度的依达拉奉注射液（E3：333μM），复方依达拉奉注射液（E3B3：依达拉奉333μM 加冰片333μM、E3B4：依达拉奉333μM加冰片1000μM）和冰片（B3：333μM、B4：1000μM）作用下，检测白介素6（IL-6）的浓度及环氧酶2（COX-2）蛋白的表达。结果：对比于假手术组、模型组动物血清炎症因子（TNF-α、IL-6）水平显著升高（P<0.01），肝功能指标（AST、ALP、TBIL）也明显增加（P<0.05）；复方依达拉奉注射液能明显降低血清TNF-α、IL-6、AST、ALP水平（P<0.05），对血清TBIL水平也具减缓作用。依达拉奉、冰片和复方依达拉奉均可降低细胞上清液IL-6、COX-2蛋白水平，以复方依达拉奉最优。结论：复方依达拉奉注射液可能通过抑制COX-2，降低促炎因子的产生，缓解肝脏的损伤而起到抗脓毒症的作用，且优于单方依达拉奉和冰片。
목적：연구복방의체랍봉주사액대농독증체내급체외모형적영향。방법：장130지SD대서수궤분위7조：가수술조（Sham）、모형조（Model）、의체랍봉저제량조（3 mg·kg-1）、의체랍봉고제량조（6 mg·kg-1）、복방의체랍봉저제량조（3.75 mg·kg-1）、복방의체랍봉고제량조（7.5 mg·kg-1）、빙편조（급여2-감순1.5 mg·kg-1）；제가수술조10지외，매조균위20지。 Sham조부개복불결찰，기여조균채용맹장결찰천공술건립대서농독증모형。술후30 min、4 h、12 h분별교차순배미정맥주사상응적약물，가수술조여모형조급여생리염수。술후6 h，검측혈청종류배사인자α（TNF-α）、백개소6（IL-6）、곡초전안매（AST）、감성린산매（ALP）화총담홍소（TBIL）수평，병관찰동물24 h생존솔。채용LPS자격소서RAW 264.7거서세포건립염증모형，재불동농도적의체랍봉주사액（E3：333μM），복방의체랍봉주사액（E3B3：의체랍봉333μM 가빙편333μM、E3B4：의체랍봉333μM가빙편1000μM）화빙편（B3：333μM、B4：1000μM）작용하，검측백개소6（IL-6）적농도급배양매2（COX-2）단백적표체。결과：대비우가수술조、모형조동물혈청염증인자（TNF-α、IL-6）수평현저승고（P<0.01），간공능지표（AST、ALP、TBIL）야명현증가（P<0.05）；복방의체랍봉주사액능명현강저혈청TNF-α、IL-6、AST、ALP수평（P<0.05），대혈청TBIL수평야구감완작용。의체랍봉、빙편화복방의체랍봉균가강저세포상청액IL-6、COX-2단백수평，이복방의체랍봉최우。결론：복방의체랍봉주사액가능통과억제COX-2，강저촉염인자적산생，완해간장적손상이기도항농독증적작용，차우우단방의체랍봉화빙편。
Objective: To explore the Compound of Edaravone injection (C.EDA) on sepsis in vivo and vitro models. Methods: One hundred and thirty SD rats were randomly divided into seven groups: sham operation group, model group, low-EDA group (L-EDA, 3 mg·kg-1), high-EDA group (H-EDA, 6 mg·kg-1), low-C.EDA group (L-C.EDA, 3.75 mg·kg-1), high- C.EDA group (H-C.EDA, 7.5 mg·kg-1) and borneol group (BOR, 1.5 mg·kg-1) with 20 rats in each group except the sham group. The septic rat models were estab-lished with cecal ligation and puncture except the sham group, the later accepted only laparotomy without ligation. At 30 min, 4 h and 12 h after the surgery, drugs were administered alternately and circularly by tail vein injection, rats in the sham and model groups were given physiological saline. The concentrations of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) were measured 6 h after the surgery, and the mortality of each group were recorded 24 h after the surgery too. RAW 264.7 cells were pretreated with LPS 1 μg to set up the inflammatory model, various concentrations of EDA (E3: edaravone 333 μM), C.EDA (E3B3:edaravone 333μM plus borneol 333μM; E3B4: edaravone 333μM plus borneol 1000μM) or borneol (B3:borneol 333μM; B4: borneol 1000μM) were administered to explore their effects on the production of IL-6 and the expression of COX-2 in these LPS-stimulated cells. Results: Compared with the sham operation group, the levels of serum inflammatory factors (TNF-α, IL-6) increased significantly (P<0.01), the liver function (AST, ALP, TBIL) was also raised (P<0.05) in the model group. The levels of serum TNF-α, IL-6, AST and ALP in the C.EDA group were notably lower than those in the model group (P<0.05), the lev-el of serum TBIL decreased slowly compared with the model group. EDA, BOR and C.EDA could decrease the activity of IL-6 and COX-2 in cell supernatant, and C.EDA was the best. Conclusion: C.EDA has antisepsis effects possibly by inhibiting the production of COX-2 and proinflammatory factors and attenuat-ing hepatic injury, and it is superior to EDA and BOR.