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

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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 establish a rat model of sepsis-induced lung injury by cecal ligation and perforation of the cecum and establish a mechanism for the regulation of pulmonary edema when detecting inflammatory responses. The above changes were detected after treatment with compound Qingxia Decoction in order to propose a possible new approach for prevention and treatment of sepsis lung injury. Methods Healthy Sprague-Dawley rats were randomly divided into 4 groups, 10 in each group: sham operation group (SHAM group), only the cecum was turned, no other treatment was performed; septic lung injury group (model group), cecal ligation and perforation induced AL (acute lung injury) I model; cecal ligation and perforation + compound Qingxia Decoction group (administered immediately after modeling, intragastric administration once a day 8 hours after the model, the dose was 10 ml/kg); cecal ligation and perforation + In the cefoperazone/sulbactam group (antibiotic Shupu deep) (intravenous injection immediately after modeling, intravenous injection once again at 8 hours after modeling, dose of 0.2 g/kg) 24 hours after the model was collected, specimens were collected. Observe the general state of the rats, measure the MPO of the lung homogenate, and take the serum of the inferior vena cava to measure the TNF-α. The pathological changes of lung tissue were observed under microscope and the changes of lung wet/dry ratio were measured. Results Compared with the SHAM group, the levels of MPO and TNF-α in the model group were significantly increased (P<0.01), pulmonary interstitial and alveolar edema, erythrocyte exudation (bleeding) and cellulose deposition, and alveolar septal capillary endothelial cells. Highly swollen. The lung wet/dry ratio was significantly increased (P<0.01). Compared with the model group, the levels of MPO and TNF-α were significantly lower (P<0.01), and the wet/dry lung ratio was significantly lower (P<0.01). The lung tissue microscopic findings: Chinese medicine treatment group and antibiotic group were narrower than the model group, the swelling of the capillary endothelial cells was relieved, the hemorrhage was relieved, and the cellulose exudation was significantly reduced. Conclusion Overexpression of cytokine TNF-α during lung injury in sepsis rats may be an important cause of lung injury caused by sepsis, while compound Qingxia Decoction can reduce lung injury during sepsis. Inhibiting the expression of TNF-α, there may be a certain link between them.
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