镰形棘豆总黄酮对特发性肺纤维化模型大鼠肺系数、白细胞分类计数及炎症因子表达的影响

Effects of total flavonoids from Oxytropis falcate Bunge. on lung coefficient,differential leukocyte count and expressions of inflammatory factors in model rats with idiopathic pulmonary fibrosis

目的研究镰形棘豆总黄酮(TFOFB)对特发性肺纤维化模型大鼠肺系数、支气管肺泡灌洗液(BALF)中白细胞分类计数及肺组织中炎症因子表达的影响。方法将60只SD大鼠采用随机数字表法分为正常对照组,模型组,醋酸泼尼松组,TFOFB低、中、高剂量组6组,每组10只。除正常对照组外,其余5组通过气管内注射以生理盐水配制的盐酸博来霉素复制特发性肺纤维化大鼠模型,造模后第15天开始,各组分别给予相应药物或生理盐水灌胃,连续灌胃4周。观察各组大鼠的一般状况,测定并比较各组大鼠的肺系数,BALF中淋巴细胞、单核细胞、嗜酸性细胞、嗜碱性细胞计数,以及肺组织中细胞间黏附分子-1(ICAM-1)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)蛋白的相对表达量。结果与正常对照组比较,模型组大鼠肺系数,BALF中淋巴细胞、单核细胞、嗜酸性细胞、嗜碱性细胞计数,以及肺组织中ICAM-1、IL-1β、MCP-1、TNF-α蛋白相对表达量明显升高,差异均有统计学意义(P<0.01);与模型组比较,醋酸泼尼松组,TFOFB中、高剂量组大鼠肺系数、BALF中白细胞分类计数及肺组织中以上炎症因子蛋白相对表达量均明显降低,TFOFB低剂量组大鼠肺组织中ICAM-1、TNF-α蛋白相对表达量明显降低,差异均有统计学意义(P<0.05或P<0.01);TFOFB高剂量组大鼠肺系数、BALF中白细胞分类计数及肺组织中以上炎症因子蛋白相对表达量明显低于TFOFB低、中剂量组,差异均有统计学意义(P <0.01)。结论TFOFB可减轻特发性肺纤维化模型大鼠的肺部炎症及肺纤维化,其作用可能与其抑制炎症细胞聚集和浸润,下调ICAM-1、IL-1β、MCP-1、TNF-α等炎症因子的表达有关。

Objective To study the effects of total flavonoids from Oxytropis falcate Bunge.( TFOFB) on lung coefficient,differential leukocyte count in bronchoalveolar lavage fluid( BALF) and expressions of inflammatory factors in lung tissues of model rats with idiopathic pulmonary fibrosis( IPF). Methods Sixty SD rats were divided into 6 groups according to random number table method,including normal control group,model group,prednisone acetate group,TFOFB low-dose,medium-dose and high-dose groups,with 10 rats in each group. Except the normal control group,the other 5 groups replicated the rats model of IPF by intratracheal injection of bleomycin hydrochloride dissolved in normal saline. From the 15 th day after establishing model,each group was given corresponding drugs or normal saline by gavage for 4 consecutive weeks. The general conditions of rats in each group were observed,and the lung coefficient,the counts of lymphocytes,monocytes,eosinophils and basophils in BALF,along with the protein relative expression quantity of intercellular adhesion molecule-1( ICAM-1),interleukin-1β( IL-1β),monocyte chemotactic protein-1( MCP-1),tumor necrosis factor-α( TNF-α) in lung tissues were measured and compared among each group. Results Compared with the rats in the normal control group,the lung coefficient,the counts of lymphocytes,monocytes,eosinophils and basophils in BALF,along with the protein relative expression quantity of ICAM-1,IL-1β,MCP-1 and TNF-α in lung tissues therein in the model group significantly increased,and the difference was statistically significant( P<0.01). Compared with the rats in the model group,the lung coefficient,differential leukocyte count in BALF and the protein relative expression quantity of the above inflammatory factors in lung tissues therein in prednisone acetate group and TFOFB medium-dose and high-dose groups all significantly decreased,the protein relative expression quantity of ICAM-1 and TNF-α in lung tissues therein in TFOFB low-dose group significantly decreased,and the differences were statistically significant( P<0.05 or P<0.01). In TFOFB high-dose group,the lung coefficient of rats,differential leukocyte count in BALF and the protein relative expression quantity of the above inflammatory factors in lung tissues were significantly lower than those in TFOFB low-dose and medium-dose groups,and the differences were statistically significant( P<0.01). Conclusion TFOFB can decrease pulmonary inflammation and attenuate pulmonary fibrosis in model rats with IPF,whose effects may be related to inhibiting inflammatory cell aggregation and infiltration and down regulating the expressions of inflammatory factors,namely ICAM-1,IL-1β,MCP-1 and TNF-α etc.