Girdin表达减少缓解博莱霉素所致小鼠肺纤维化的调节及肺组织中p65、TGF-β的影响

Effects of Reduced Girdin on Bleomycin-Induced Pulmonary Fibrosis, p65 and TGF-β in Pulmonary Tissues of Mice

目的探究微丝附着梁蛋白(Girdin)表达减少对博莱霉素(Bleomycin,BLM)所致小鼠肺纤维化及肺组织中核因子p65、转化生长因子β(TGF-β)的影响.方法昆明小鼠分为对照组(Control)、模型组(3 mg/kg BLM)、阴性对照组(shRNA-NC)、干扰组(Girdin-shRNA1、2、3),比较各组肺组织损伤情况、纤维化标记物蛋白表达、P65磷酸化水平及炎性因子水平.结果与Control组比较,BLM组Girdin mRNA水平显著升高(P<0.05);与BLM组比较,Girdin-shRNA1、2、3组Girdin mRNA水平明显降低(P<0.05),其中Girdin-shRNA1组降低效果最显著,后续实验选用Girdin-shRNA1.与BLM组比较,Girdin-shR-NA1组肺损伤评分、肺组织湿/干重比值、Girdin、纤连蛋白(Fibronectin)、α-平滑肌激动蛋白(α-SMA)、TGF-β、p65磷酸化水平、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平显著降低,IL-4水平显著升高(P<0.05).结论Girdin表达减少可缓解BLM所致小鼠肺纤维化,可能与减少细胞外基质分泌、降低炎症反应有关.

Objective To explore the effects of decreased girders of actin filaments(Girdin)on bleomyein(BLM)-induced pulmonary fibrosis,muclear factor p65 and transforming growth factorβ(TGF-β)in pulmonary tissues of mice.Methods Kunming mice were divided into a control group(Control),a model group(3 mg/kg BLM),a negative control group(shRNA-NC)and an interference group(Girdin-shRNA 1,2,3).The damage of pulmonary tissues,the expression of fibrosis marker proteins,phosphorylation level of P65 and the level of inflammatory factors were compared among all groups.Results Compared with the control group,Girdin mRNA level in BLM group was significantly increased(P<0.05).Compared with BLM group,level of Girdin mRNA in Girdin-shRNA 1,2 and 3 groups was significantly decreased(P<0.05),with the decrease being the most signifcant in Girdin-shRNA1 group.Girdin-shRNA1 was used in the subsequent experi-ments.Compared with BLM group,pulmonary injury score,wet/dry weight(W/D)ratio in pul-monary tissues,Girdin,fibronectin,a-smooth muscle agonist protein(α-SMA),TGF-β,phos-phorylation level of p65,tumor necrosis factor α(TNF-α)and interleukin 6(IL6)levels were signifieantly decreased in Girdin-shRNA1 group,while IL-4 level was significantly increased(P<0.05).Conclusion The decreased Girdin expression could alleviate BLM-induced pulmonary fibro-sis in mice,and the effect might be related to reduced secretion of extracellular matrix and de-creased inflammatory responses.