帕夫林通过抑制NLRP3形成减轻博莱霉素诱导的小鼠肺纤维化  

Paeoniflorin attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing NLRP3 inflammasome formation

作　　者：许容容 孔辉 徐健 陈雪松 朱晓莉[1] 解卫平 

机构地区：[1]东南大学附属中大医院呼吸内科,江苏南京210009 [2]南京医科大学第一附属医院呼吸与危重症医学科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2017年第7期799-803,841,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81273571);江苏省呼吸病临床医学研究中心(BL2012012)

摘　　要：目的:探讨帕夫林(paeoniflorin,PA)对博莱霉素(bleomycin,BLM)诱导的小鼠肺纤维化的影响及其作用机制。方法:将60只SPF级雄性C57BL/6小鼠随机分为4组:对照组(sham operation,SH)、对照组+帕夫林组(SH+PA)、模型组(BLM)、模型组+帕夫林(BLM+PA);气管内滴注博莱霉素(2 mg/kg)建立小鼠肺纤维化模型,对照组气管内滴注生理盐水,从造模当天开始,SH+PA、BLM+PA组小鼠每日给予50 mg/kg帕夫林灌胃,SH、BLM组小鼠每日给予等量生理盐水灌胃;在造模第14天处死小鼠,留取小鼠肺组织。记录各组小鼠体重变化;统计各组小鼠生存率;HE染色法观察小鼠肺组织纤维化程度;肺组织匀浆羟脯氨酸定量评估肺组织胶原蛋白含量;ELISA法测定肺组织匀浆中白介素(interleukin,IL)-18、IL-1β含量;Western blot法检测肺组织匀浆中NLRP3、转化生长因子β1(transforming growth factor-β1,TGF-β1)表达水平。结果:与对照组相比,帕夫林可显著提高小鼠生存率;经帕夫林治疗14 d后,小鼠肺组织纤维化病变较模型组减轻;小鼠肺组织胶原蛋白含量显著降低(P<0.05);小鼠外周血及肺组织中IL-18、IL-1β含量较模型组相比明显减少(P<0.05);与模型组相比,NLRP3蛋白水平以及TGF-β1蛋白表达水平显著下调(P<0.05)。结论:帕夫林可减轻博莱霉素诱导的小鼠肺纤维化程度,其作用可能是通过抑制NLRP3炎症小体的形成发挥的。Objective：To investigate the therapeutics effect and the potential mechanism of paeoniflorin on the bleomycin-induced pulmonary fibrosis in mice. Methods：Sixty adult male SPF C57BL/6 mice were randomly divided into four groups：the control group （Sham operation,SH）,the control＋paeoniflorin group （SH＋PA）,the bleomycin group （BLM） and the bleomycin＋paeoniflorin group （BLM＋PA）. From the day of operation,the mice of the SH＋PA and BLM＋PA groups were treated with paeoniflorin intragastrically （50 mg/kg,daily） while the mice of the SH and BLM groups were given the same volume of normal saline. The model of pulmonary fibrosis was established through intratracheally instillation with bleomycin （2 mg/kg） except for the control group,in which normal saline was used. All the samples were sacrificed on the day 14 after operation, and the change of body weight and mortality rates of each group were analyzed. The pathological section of lung tissues were harvested for hemotoxylin and eosin stain. Collagen deposition in the lung was determined by measuring the total hydroxyproline content. ELISA was performed to analyze the level of IL-18 and IL- 1β in the lung homogenates. The levels of NLRP3 and TGF-β1 in the lung were detected by Western blotting. Results：Paeoniflorin significantly increased the survival rate and attenuated the collagen deposition in the bleomycin-induced pulmonary fibrosis mouse model compared with the control group （P〈0.05）. The IL-18 and IL-1β in the lung homogenates were decreased notably after administration of paeoniflorin,when compared to the control group （P〈0.05）. The expression of NLRP3 and TGF-βI were down regulated significantly （P〈0.05）. Conclusion：Paeoniflorin may attenuate bleomycin-induced pulmonary fibrosis in mice by suppressing NLRP3 inflammsome formation.

关 键 词：帕夫林 肺纤维化 NLRP3 博莱霉素 

分 类 号：R563[医药卫生—呼吸系统]