摘要
目的探讨肺纤方通过调控高迁移率族蛋白1(high mobility group protein 1,HMGB1)/Toll蛋白受体2(toll protein receptor 2,TLR2)信号通路对特发性肺纤维化的抑制作用。方法选取健康雄性SD大鼠80只,分为对照组16只和造模组64只。造模组采用博来霉素气管注射法建立特发性肺纤维化模型,对照组给予等量生理盐水气管注射。造模成功后,将造模组大鼠随机分为模型组、肺纤方低、高浓度组及泼尼松组,各16只。模型组和对照组分别给予生理盐水10 mL/kg,1次/d,灌胃给药;肺纤方低、高浓度组分别给予0.72、2.9 g/mL肺纤方药液10 mL/kg,1次/d,灌胃给药;泼尼松组给予1.0 mg/mL醋酸泼尼松溶液10 mL/kg,1次/d,灌胃给药。所有大鼠均连续给药4周。对大鼠肺纤维化程度、血清血小板衍生生长因子(platelet-derived growth factor,PDGF)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)及肺泡灌洗液炎症因子水平、肺组织HMGB1、TLR2蛋白表达水平进行检测。结果治疗后,与模型组比较,各组大鼠肺纤维化程度评分较低,肺泡灌洗液肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)水平较低,血清PDGF、TGF-β1水平较低,肺组织HMGB1、TLR2蛋白表达水平较低,且肺纤方低浓度组>泼尼松组>肺纤方高浓度组,差异有统计学意义(P<0.05)。结论肺纤方能明显减轻特发性肺纤维化模型大鼠肺纤维化程度,降低血清细胞因子PDGF、TGF-β1水平,抑制肺部炎症反应,且药物浓度越高效果越明显,其作用可能与下调HMGB1/TLR2信号通路活性有关。
Objective To analyze the inhibitory effect of Feixian Formula(肺纤方)on idiopathic pulmonary fibrosis by regulating the signaling pathway of high mobility group protein 1(HMGB1)/Toll protein receptor 2(TLR2).Methods Eighty healthy male SD rats were selected,which were divided into control group with 16 rats and modeling group with 64 rats.Idiopathic pulmonary fibrosis models were established by intratracheal injection of bleomycin in the modeling group,and rats in the control group were given the same amount of saline by intratracheal injection.After the establishment of the model,rats in the modeling group were randomly divided into model group,Feixian Formula low-concentration group,Feixian Formula high-concentration group and prednisone group,each with 16 rats.Rats in the model group and the control group were respectively given physiological saline 10 mL/kg by intragastric administration,once a day.Rats in the Feixian Formula low-concentration group,Feixian Formula high-concentration group were respectively given 0.72 g/mL,2.9 g/mL Feixian Formula solution 10 mL/kg by intragastric administration,once a day.Rats in the prednisone group were given 1.0 mg/mL prednisone acetate solution 10 mL/kg by intragastric administration,once a day.All rats were given 4 weeks of continuous administration.The degree of pulmonary fibrosis,serum levels of platelet-derived growth factor(PDGF)and transforming growth factor-β1(TGF-β1)and levels of inflammatory factors in alveolar lavage fluid,expressions of HMGB1 and TLR2 protein in lung tissue were detected.Results After treatment,compared with those of the model group,the pulmonary fibrosis scores were lower in each group,the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)in alveolar lavage fluid were lower,serum levels of PDGF and TGF-β1 were lower,the expression levels of HMGB1 and TLR2 protein in lung tissue were lower,and the order was Feixian Formula low-concentration group>prednisone group>Feixian Formula high-concentration group,and the difference was statistically significant(P<0.05).Conclusions Feixian Formula can significantly reduce the degree of pulmonary fibrosis in rats with idiopathic pulmonary fibrosis,reduce the levels of serum cytokines PDGF and TGF-β1,inhibit inflammation in the lungs and the higher the drug concentration is,the more significant the effect is.The effect may be related to down-regulation of HMGB1/TLR2 signaling pathway activity.
作者
钟昌会
冼丽娜
钱进
肖行
杨远征
陈伟
ZHONG Changhui;XIAN Lina;QIAN Jin;XIAO Xing;YANG Yuanzheng;CHEN Wei(The First Affiliated Hospital of Hainan Medical College,Haikou 570100,Hainan,China)
出处
《中华中医药学刊》
CAS
北大核心
2023年第4期55-59,I0015,共6页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81760341)。
作者简介
钟昌会(1987-),海南万宁人,主治医师,学士,研究方向:重症呼吸系统;通讯作者:陈伟(1981-),女,山东日照人,副主任医师,博士,研究方向:重症呼吸系统。
