摘要
目的探索桃红四物汤通过酪氨酸激酶2/信号传导与转录激活子3(Janus kinase 2/signal transducing activator of transcription,JAK2/STAT3)信号通路对肺纤维化模型大鼠凋亡及EMT的影响。方法将40只SD大鼠随机分为正常组、模型组、甲泼尼龙组、桃红四物汤低浓度组、桃红四物汤高浓度组,每组8只,气管内滴入博来霉素(bleomycin,BLM)建立IPF模型。HE及Masson染色观察肺组织形态学改变;ELISA检测大鼠血清MMP-7、TGFβ-1、TNF-α的含量;免疫组化和Western blot测定肺组织JAK2、p-JAK2、STAT3、p-STAT3、E-cadherin、α-SMA蛋白的表达;RT-PCR检测肺组织JAK2、STAT3、Bcl-2、Bax基因表达。结果与正常组相比,模型组大鼠肺泡炎症和纤维化程度,血清中TNF-α、MMP-7、TGFβ-1的含量,肺组织JAK2、p-JAK2、STAT3、p-STAT3、α-SMA蛋白表达,JAK2、STAT3、Bax基因表达水平均升高,Bcl-2基因及E-cadherin蛋白表达水平均降低。与模型组相比,桃红四物汤高浓度组大鼠肺组织肺泡炎症和纤维化程度,血清中TNF-α、MMP-7、TGFβ-1的含量,肺组织JAK2、p-JAK2、STAT3、p-STAT3、α-SMA蛋白表达,JAK2、STAT3、Bax基因表达水平均降低,Bcl-2基因及E-cadherin蛋白表达升高。结论桃红四物汤可能通过抑制JAK2/STAT3信号通路,下调Bax、α-SMA和上调Bcl-2、E-cadherin的表达诱导肺纤维化模型大鼠凋亡及EMT,从而发挥抗肺纤维化作用。
Aim To explore the effect of Taohong Siwu Decoction on apoptosis and EMT of pulmonary fibrosis model rats by JAK2/STAT3 signaling pathway.Methods Forty SD rats were randomly divided into control group,model group,methylprednisolone group,Taohong Siwu Decoction low-concentration,high-concentration group respectively,with eight cases in each group.The intratracheal injection of bleomycin was applied to induce IPF rat models.HE and Masson staining were performed to observe the pathological changes of lung tissues in each group.ELISA was used to detect the contents of TNF-α,MMP-7 and TGFβ-1 in serum of rats.Immunohistochemistry and Western blot were applied to detect the protein expression of JAK2,p-JAK2,STAT3,p-STAT3,E-cadherin,α-SMA in lung tissues.RT-PCR was applied to detect the expression of JAK2,STAT3,Bcl2 and Bax genes in lung tissues.Results Compared with control group,the degree of alveolar inflammation and fibrosis degree,the contents of TNF-α,MMP-7 and TGFβ-1 in serum,the levels of JAK2,p-JAK2,STAT3,p-STAT3,α-SMA protein expression,JAK2,STAT3,Bax gene expression were up-regulated,and the levels of Bcl-2 gene and E-cadherin protein expression were down-regulated in lung tissues.Compared with model group,the degree of alveolar inflammation and fibrosis,the contents of TNF-α,MMP-7 and TGFβ-1 in serum,the levels of JAK2,p-JAK2,STAT3,p-STAT3,α-SMA protein expression,JAK2,STAT3 and Bax gene expression were reduced,while the levels of Bcl-2 gene and E-cadherin protein expression were elevated in Taohong Siwu Decoction high-concentration group.Conclusions Taohong Siwu Decoction may regulate JAK2/STAT3 signaling pathway,down-regulate Bax,α-SMA and up-regulate Bcl-2,E-cadherin expression to induce apoptosis and EMT in rat model of pulmonary fibrosis,thus playing an anti-pulmonary fibrosis role.
作者
欧慧萍
吴趋荟
袁多
林辉
何聪睿
李妲
范伏元
OU Hui-ping;WU Qu-hui;YUAN Duo;LIN Hui;HE Cong-rui;LI Da;FAN Fu-yuan(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan Traditional Chinese Medicine College,Zhuzhou,Hunan 412000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第8期1577-1583,共7页
Chinese Pharmacological Bulletin
基金
湖南省自然科学基金资助项目(No 2023JJ60243)
湖南省教育厅科学研究项目(No 19C1446)
湖南省中医药科研计划重点项目(No 2021038)
湖南省教育厅青年项目(No 20B442)。
