摘要
目的研究维替泊芬(verteporfin,VP)对肺纤维化小鼠的治疗作用及其机制。方法给予C57BL/6小鼠气管内注射博来霉素(bleomycin,BLM)建立肺纤维化模型。造模后第8天开始使用VP(100 mg·kg-1)治疗,每3天腹腔注射一次,连续给药两周。于造模后第21天处死小鼠,计算体重变化率和肺系数;采用HE染色和Masson染色观察小鼠肺部的纤维化病变;羟脯氨酸(hydroxyproline,HYP)试剂盒测定肺组织的HYP水平;q-PCR检测α-平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)、Yes相关蛋白(Yes-associated protein,YAP)和白细胞介素11(interleukin-11,IL-11)mRNA表达水平;Western blot法检测Ⅰ型胶原蛋白(CollagenⅠ)、α-SMA、YAP和核因子κB p65(nuclear factor kappa-B,NF-κB p65)的蛋白表达水平;ELISA试剂盒检测肺组织匀浆中IL-11水平。结果经过VP治疗后,小鼠的体重变化率和肺系数降低;HE染色和Masson染色中的纤维化病变及胶原沉积有改善;肺组织的HYP、CollagenⅠ和α-SMA水平降低;VP也降低了肺组织中YAP、NF-κB p65和IL-11的表达。结论VP可减轻BLM诱导的小鼠肺纤维化,其治疗作用与IL-11的下调相关。
Objective To investigate the therapeutic effect and mechanisms of verteporfin(VP)on pulmonary fibrosis mice.Methods The pulmonary fibrosis models were established by intra-tracheal injections of bleomycin(BLM)into C57BL/6 mice.VP(100 mgkg-1)treatment began on the 8th day after BLM injection,and intraperitoneal injections were given every 3 days for two weeks.The mice were executed on the 21st day.The wet weight of the lungs and the rate of weight change were recorded;the fibrotic foci and collagen deposition in the lungs were observed by HE staining and Masson staining;the hydroxyproline(HYP)levels in the lung tissues were measured by an HYP kit;the mRNA levels of Alpha-smooth muscle actin(α-SMA),the Yes-associated protein(YAP)and interleukin-11(IL-11)were measured by q-PCR;the protein levels of Collagen Ⅰ,α-SMA,YAP,and NF-κB p65 were measured by Western blot;the IL-11 levels in lung tissue homogenates were measured by an ELISA kit.Results After VP treatments,the rate of body weight change and the lung-body ratio of mice were reduced;the fibrotic foci and collagen deposition were improved in HE staining and Masson staining;the levels of HYP,CollagenⅠandα-SMA in lung tissues were reduced;VP also decreased the expressions of YAP,NF-κB p65 and IL-11 in lung tissues.Conclusion VP alleviates BLM-induced pulmonary fibrosis in mice,and its effects may be related to the downregulation of IL-11.
作者
阎秋雨
陆晓萱
旷喜
杜俊蓉
YAN Qiuyu;LU Xiaoxuan;KUANG Xi∗;DU Junrong(West China School of Pharmacy,Sichuan University,Sichuan 610041,China)
出处
《沈阳药科大学学报》
CAS
CSCD
2024年第1期96-101,共6页
Journal of Shenyang Pharmaceutical University
基金
成都中医药大学西南特色中药资源重点实验室开放研究基金资助项目(2019LF3016)。
