脂多糖性肺损伤大鼠血清白细胞介素1β和白细胞介素8的变化及低剂量环磷酰胺的干预作用

Changes of serum interleukin-1 beta and interleukin-8 in pulmonary injury rats induced by lipopolysaccharide and the interventional effects of low-dose cyclophosphamide

目的:观察低剂量环磷酰胺对脂多糖性肺损伤模型大鼠血白细胞介素1β和白细胞介素8的影响,并与地塞米松进行阳性对照。方法:实验于2003-03/12在遵义医学院外科动物实验室、中心实验、病理实验室进行。取160只SD大鼠随机分为4组(n=40):环磷酰胺组、模型组、地塞米松组和生理盐水组。除生理盐水组外,其他3组大鼠采用腹腔注射内毒素脂多糖5mg/kg制作肺损伤模型。注射脂多糖后,环磷酰胺组立即腹腔注射1mL环磷酰胺(4mg/kg);地塞米松组腹腔注射1mL地塞米松(5mg/kg);模型组腹腔注射1mL生理盐水。生理盐水组腹腔注射生理盐水2mL。各组于模型制作后第1,4,6,8小时分别取10只采血,以ELISA法测血清中白细胞介素1β和白细胞介素8水平,且于第6小时留取肺组织进行肺组织的病理学光镜检查。结果:160只大鼠全部进入结果分析。①肺组织的病理学变化:模型组大鼠肺泡腔见大量出血及炎性细胞浸润,支气管上皮剥脱、水肿等,环磷酰胺组和地塞米松组也可见炎细胞浸润、肺萎陷现象,与模型组比较,明显减轻(P<0.05)。②白细胞介素1β水平:模型组、环磷酰胺组和地塞米松组脂多糖腹腔注射后1h已显著高于生理盐水组,6h达到峰值(P<0.05);环磷酰胺组和地塞米松组各时间点均低于模型组(P<0.05),但两组间差异不显著(P>0.05)。③白细胞介素8水平:模型组、环磷酰胺组和地塞米松组脂多糖腹腔注射后1h已显著高于生理盐水组,8h达到峰值(P<0.05);环磷酰胺组和地塞米松组各时间点均低于模型组(P<0.05),但两组间差异不显著(P>0.05)。结论:低剂量环磷酰胺与地塞米松一样具有明显的抗炎作用,能降低肺损伤大鼠血清白细胞介素1β和白细胞介素8水平,减轻其肺组织损害。

AIM： To explore the effect of a low-dose cyclophosphamide （CY）on the serum interleukin （IL）-1 ,IL-8 in pulmonary injury rats induced by lipopolysaccharide （LPS） and perform positive control with desamethasone （DEX）. METHODS： The experiment was completed at the Animal Laboratory of Surgery, Central Lab, Laboratory of Pathology, Zunyi Medical College from March to December 2003. 160 SD rats were divided into 4 groups randomly （n=40）： CY group, model group, DEX group and saline group. Except saline group, the pulmonary injury models were made by injecting LPS （5 mg/kg） into abdominal cavity of rats in the other three groups. After LPS injected, 1 mL CY was injected into abdominal cavity immediately in CY group; 1 mL DEX was injected into abdominal cavity immediately in DEX group; 1 mL saline was injected into abdominal cavity immediately in the model group; 2 mL saline was injected into abdominal cavity immediately in saline group. Blood samples were obtained in the 1^th, 4^th, 6^th and 8^th hours after LPS injected, and the serum IL-1β and IL-8 were measured by ELISA, and the specimens of lung tissues were reserved at the 6^th hour. RESULTS： Totally 160 rats were involved in the result analysis. ① Pathological change in pulmonary tissue： The evidence of pulmonary injury-neutrophil infiltration and hemorrhage in the cavity of alveolus, bronchiole epithelial desquamation, edema and so on were found in sections of the model group. Neutrophil infiltration and alveolar atelectasis in CY group and DEX group, compared with the model group, alleviated （P 〈 0.05 ）. ②Level of IL-1β： Compared with the saline group, the serum IL-1β increased obviously in other three groups after LPS injected （P 〈 0.05）. And compared with the model group, the serum IL-1β decreased markedly in the CY group and DEX group （P 〈 0.05）. No signilqcant difference was found of the serum IL-1βin the two groups （P 〉 0.05）. ③Level of IL-8： Compared with the saline group, the serum IL-8 increased obviously in other three groups after LPS injected （P 〈 0.05）,And compared with the model group, the serum IL-8 decreased markedly in the CY group and DEX group （p 〈 0.05）. No Significant difference was found of the serum IL-8 in the two groups （P〈 0.05）. CONCLUSION： Same as the DEX, the low-dose CY plays an important role on anti-inflammation and can decrease serum IL-1β and IL-8 levels in pulmonary injury rats and relieve it＇s pulmonary injury.