复方清下汤对脓毒症大鼠细胞因子调控及其肺损伤的作用

Role of Fufang Qingxia Tang(Compound Qingxia Decoction) in modulation of cytokines on sepsis-induced acute lung injury

目的盲肠结扎穿孔导致大肠埃希菌腹膜炎进而建立脓毒症肺损伤大鼠模型,检测炎性反应时,细胞因子的调控变化,探讨肺水肿的形成机制。经复方清下汤处理后检测上述变化,以期为脓毒症肺损伤的防治提出可能的新途径。方法将健康SD大鼠随机分为4组,每组10只:假手术组(SHAM组),只翻动盲肠,不做其他处理;脓毒症肺损伤组(模型组),盲肠结扎穿孔诱发AL(急性肺损伤)I模型;盲肠结扎穿孔+复方清下汤组(造模后立即灌胃给药,造模后8 h再次灌胃1次,剂量为10 m l/kg);盲肠结扎穿孔+头孢哌酮/舒巴坦组(抗生素舒普深)(造模后立即静脉注射1次,造模后8 h再次静脉注射1次,剂量为0.2 g/kg)造模24 h后收集标本。分别观察大鼠的一般状态,肺组织匀浆MPO的测定,留取下腔静脉血清进行TNF-α的测定。镜下观察肺组织病理形态学改变,测量肺湿/干比值的变化。结果与SHAM组比较,模型组MPO、TNF-α水平明显升高(P<0.01),肺间质和肺泡内水肿,伴大量红细胞渗出(出血)和纤维素沉积,肺泡间隔毛细血管内皮细胞高度肿胀。肺湿/干比值明显增加(P<0.01),抗生素及中药处理组与模型组比较,MPO、TNF-α水平明显降低(P<0.01),肺湿/干比值明显降低(P<0.01),肺组织镜下表现:中药处理组及抗生素组较模型组肺泡间隔变窄,毛细血管内皮细胞肿胀减轻,出血减轻,纤维素渗出明显减少。结论脓毒症大鼠肺损伤时细胞因子TNF-α过度表达,炎性介质的过度表达可能是造成脓毒症肺损伤的重要原因,而复方清下汤可以减轻脓毒症时的肺损伤和抑制TNF-α的表达,它们之间可能存在一定的联系。

Objective To investigate the modulation of TNF-α and MPO on sepsis-inducod acute lung injury （ALI） and the role of Fufang Qingxia Tang （FFQX）. Method SD rats were randomly divided into four groups： SHAM group （n = 10） which didn＇t undergo any operation, ALI group （n = 10） which received cecal ligation and puncture to induce the ALI model, FFQX group （n = 10） which was administered FFQX （ 10 mg/kg） by gavage immediately and 8 hours after model establishment respectively, and Antibiotics group （ALI ＋ Cefoperazone-Sulbactam, pfizer, n = 10） which was administered Cefoperazone-Sulbactam （0.2 g/kg） by intravenous injection immediately and 8 hours after model establishmerit respectively. Specimen were collected 24 hours after the establishment of ALI model. Result The levels of serum TNF-α and MPO in ALI group were significantly increased compared with SHAM group （ P 〈 0.01 ）. Pulmonary interstitial and intra-alveolar edema with exudate of RBCs and deposit of fibrin were seen. Endothelial cell of alveolar septum capillaries were obviously swollen. The ratio of W/D in ALI group was higher than that in SHAM group （ P 〈 0.01 ）. Compared with ALl group, the level of serum TNF-α and MPO in homogenate were significantly decreased and the ratio of W/D was lower in FFQX group and antibiotics group （P 〈 0.01 each）. Narrowed alveolar septum, slight endothelial cell swelling and decreased bleeding and exudate were seen in both FFQX group and antibiotics group. Conclusion Our research revealed that overexpression of several major inflammatory factors such as TNF-α in sepsis-induced ALI rat model may be the cause of sepsis-induced ALL FFQX can decrease the secretion of TNF-α and alleviate the extent of sepsis-induced acute lung injury .