摘要
目的探讨山姜素(ALPN)对博来霉素(BLM)诱导的小鼠肺纤维化的影响及其作用机制。方法将小鼠随机分为对照组、模型组(气管内滴注BLM)、低高剂量ALPN组(L-ALPN组)和高剂量ALPN组(H-ALPN组)(分别每日灌胃10 mg/kg或30 mg/kg ALPN),每组10只小鼠。收集肺组织,HE和Masson染色观察肺泡结构和病理形态;RT-qPCR、免疫组织化学染色和Western blot分别检测肺组织中Ⅰ型胶原蛋白(collagenⅠ)、转化生长因子β1(TGF-β1)、钙黏附蛋白E(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)、蛋白激酶R样内质网激酶(PERK)、p-PERK、C/EBP同源蛋白(CHOP)和葡萄糖调节蛋白78(GRP78)的mRNA和蛋白表达。结果与对照组比较,模型组小鼠的肺呈现纤维化改变,肺组织中collagenⅠ、TGF-β1、α-SMA、p-PERK/PERK、CHOP和GRP78的表达均明显升高(P<0.01),E-cadherin表达明显降低(P<0.01);与模型组比较,低和高剂量ALPN组小鼠的肺纤维化均明显改善,肺组织中collagenⅠ、TGF-β1、α-SMA、p-PERK/PERK、CHOP和GRP78的表达均明显降低(P<0.05或P<0.01),E-cadherin表达明显升高(P<0.05或P<0.01)。结论ALPN能缓解BLM诱导的肺纤维化,可能与其抑制内质网应激有关。
Objective To investigate the effect and potential mechanism of alpinetin(ALPN)on bleomycin(BLM)-induced pulmonary fibrosis in mice.Methods The mice were randomly divided into control group,model group(intratracheally instilled BLM),low-dose(L-ALPN group)and high-dose ALPN groups(H-ALPN group)(10 mg/kg or 30 mg/kg ALPN daily,respectively)with 10 in each.Lung tissues were collected,and the alveolar structure and pathological morphology were microscopied by HE and Masson staining;mRNA and protein expressions of collagenⅠ,TGF-β1,E-cadherin,α-SMA,p-PERK,PERK,CHOP and GRP78 in lung tissue were detected by RT-qPCR,immunohistochemistry and Western blot,respectively.Results Compared with control group,the lung of the model group showed fibrotic changes,and the expression of collagenⅠ,TGF-β1,α-SMA,p-PERK/PERK,CHOP and GRP78 in lung tissue was significantly increased(P<0.01).E-cadherin expression was significantly decreased(P<0.01).Compared with model group,pulmonary fibrosis was significantly alleviated in low and high doses ALPN groups,the expression of collagenⅠ,TGF-β1,α-SMA,p-PERK/PERK,CHOP and GRP78 in lung tissue were significantly decreased(P<0.05 or P<0.01),and the expressionof E-cadherin was significantly increased(P<0.05 or P<0.01).Conclusions ALPN may alleviate BLM-induced pulmonary fibrosis,and this effect may be attributed to the inhibition of endoplasmic reticulum stress.
作者
司常星
丁艳艳
尹凤先
SI Changxing;DING Yanyan;YIN Fengxian(Department of Respiratory and Critical Care Medicine,Beijing Daxing District People′s Hospital,Beijing 102600,China)
出处
《基础医学与临床》
2023年第12期1827-1833,共7页
Basic and Clinical Medicine
关键词
山姜素
博来霉素
内质网应激
肺纤维化
alpinetin
bleomycin
endoplasmic reticulum stress
pulmonary fibrosis