详细信息

基于STAT6/PPAR-γ通路探讨升陷化纤方及其拆方调控M2型巨噬细胞极化对肺纤维化的影响    

Exploration on the Effects of Shengxian Huaxian Prescription on Pulmonary Fibrosis with Regulating the Polarization of M2 Type Macrophages Based on STAT6/PPAR-γ Pathway

文献类型:期刊文献

中文题名:基于STAT6/PPAR-γ通路探讨升陷化纤方及其拆方调控M2型巨噬细胞极化对肺纤维化的影响

英文题名:Exploration on the Effects of Shengxian Huaxian Prescription on Pulmonary Fibrosis with Regulating the Polarization of M2 Type Macrophages Based on STAT6/PPAR-γ Pathway

作者:杨虹[1];周世欣[2];李红梅[1];武妍琳[1];刘喜平[2];朱中博[2];张旭辉[1,3]

第一作者:杨虹

机构:[1]甘肃中医药大学附属医院,甘肃兰州730000;[2]甘肃中医药大学,甘肃省中药新产品创制工程实验室,甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000;[3]甘肃中医药大学第三附属医院,甘肃白银730900

第一机构:甘肃中医药大学第二附属医院

年份:2025

卷号:32

期号:1

起止页码:113

中文期刊名:中国中医药信息杂志

外文期刊名:Chinese Journal of Information on Traditional Chinese Medicine

收录:CSTPCD

基金:国家自然科学基金(82260889);兰州市城关区科技计划项目(2021SHFZ0026)。

语种:中文

中文关键词:肺纤维化;升陷化纤方;巨噬细胞极化;STAT6/PPAR-γ通路;大鼠

外文关键词:pulmonary fibrosis;Shengxian Huaxian Prescription;macrophage polarization;STAT6/PPAR-γ pathway;rats

摘要:目的观察升陷化纤方及其拆方抗肺纤维化的协同效应,探讨其机制是否与调控STAT6/PPAR-γ通路促进M2型巨噬细胞向M1型极化有关。方法从70只SD大鼠中随机抽取10只作为空白组,剩余大鼠气管内滴注博来霉素建立肺纤维化模型,并随机分为模型组、阳性药组、全方组、升陷组、通络组、补肾组,每组10只,全方组、升陷组、通络组、补肾组分别予相应药液12.60、7.65、3.60、2.25g/kg灌胃,阳性药组予吡非尼酮混悬液0.12g/kg灌胃,空白组及模型组予等体积生理盐水灌胃,1次/d,连续28d。检测大鼠肺功能,ELISA测定大鼠血清白细胞介素(IL)-6、转化生长因子(TGF)-β1含量,Masson染色观察肺组织形态,免疫荧光染色测定肺组织CD68、诱导型一氧化氮合酶(iNOS)及CD206、精氨酸酶-1(Arg-1)表达,Western blot测定肺组织细胞因子信号抑制物(SOCS)1、SOCS3、信号传导及转录激活因子(STAT)6、p-STAT6、过氧化物酶体增殖物激活受体(PPAR)-γ蛋白表达。结果与空白组比较,模型组大鼠呼气峰流速(PEF)、吸气峰流速(PIF)、呼出50%潮气量时呼气流速(EF50)明显降低,血清IL-6、TGF-β1含量明显升高,Masson染色可见肺组织大量胶原纤维沉积,Ashcroft评分明显升高,CD206、Arg-1、STAT6、p-STAT6、PPAR-γ蛋白表达明显升高(P<0.01),SOCS1、SOCS3蛋白表达明显降低(P<0.01),CD68、iNOS表达未见明显变化(P>0.05);与模型组比较,各给药组大鼠PEF、PIF、EF50明显升高,血清IL-6、TGF-β1含量明显降低,肺组织胶原纤维沉积不同程度减少,Ashcroft评分明显降低,CD206、Arg-1、STAT6、p-STAT6、PPAR-γ蛋白表达明显降低(P<0.01),CD68、iNOS、SOCS1、SOCS3蛋白表达明显升高(P<0.05),上述指标均以全方组变化最明显,升陷组次之(P<0.01,P<0.05)。结论升陷化纤方及其拆方均有抗肺纤维化作用,其机制与调控STAT6/PPAR-γ通路,促进M2型巨噬细胞向M1型极化有关。全方组效果最佳,升陷组在方中发挥重要作用,各组间配伍具有协同效应。
Objective To observe the synergistic effect of Shengxian Huaxian Prescription and its disassembled prescription on pulmonary fibrosis;To explore whether its mechanism is related to regulating the STAT6/PPARγ pathway to promote polarization of M2 type macrophages towards M1 type.Methods Ten SD rats were randomly selected from 70 rats as blank group,and the remaining rats were re-established pulmonary fibrosis model by intratracheal infusion of bleomycin.After modeling,the rats were divided into model group,positive group,Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group,with 10 rats in each group.Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group were given 12.60,7.65,3.60 and 2.25 g/kg of corresponding TCM solution,respectively;the positive group was given 0.12 g/kg of pirfenidone suspension;the blank group and the model group were given equal volume of normal saline,once a day,for consecutive 28 days.The lung function of rats was detected,the contents of IL-6 and TGF-β1 in serum were detected by ELISA,the pathological changes in lung tissue were observed by Masson staining,the expression of CD68,iNOS and CD206,Arg-1 in lung tissue were detected by immunofluorescence,the expression of SOCS1,SOCS3,STAT6,p-STAT6 and PPAR-γ in lung tissue were detected by Western blot.Results Compared with the blank group,the PEF,PIF and EF50 in model group rats significantly decreased,and the contents of serum IL-6 and TGF-β1 significantly increased,Masson staining showed a large amount of collagen fiber deposition,Ashcroft score significantly increased,CD206,Arg-1,STAT6,p-STAT6,PPARγ protein expression significantly increased(P<0.01),the expressions of SOCS1 and SOCS3 protein significantly decreased(P<0.01),while the expression of CD68 and iNOS were not significantly changed(P>0.05).Compared with the model group,the PEF,PIF and EF50 in all administration groups significantly increased,and the contents of serum IL-6 and TGF-β1 significantly decreased,collagen fiber deposition in lung tissue were decreased to varying degree,Ashcroft score significantly decreased,the expression of CD206,Arg-1,STAT6,p-STAT6 and PPAR-γ protein significantly decreased(P<0.01),the expressions of CD68,iNOS,SOCS1 and SOCS3 protein significantly increased(P<0.05).The above indicators showed the most significant changes in Shengxian Huaxian Prescription group,followed by Shengxian group(P<0.01,P<0.05).Conclusion Both Shengxian Huaxian Prescription and its disassembled prescription have anti pulmonary fibrosis effects,and their mechanism may related to regulating the STAT6/PPAR-γ pathway and promoting polarization of M2 type macrophages towards M1 type.Shengxian Huaxian Prescription group has the best effect,while Shengxian group play an important role in the prescription,and the compatibility between each group has a synergistic effect.

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