Abstract Objective To investigate the effect of Chinese ginkgo biloba extract (GBE) on NOTCH1 signaling pathway in bleomycin-induced pulmonary fibrosis in animal models, to explore medicine mechanisms of GBE in treatment of pulmonary fibrosis. Methods Twenty-five Kunming mice were randomly divided into 5 groups: control group, model group, GBE group, GBE-NOTCH1-shRNA group,negative plasmids group(n=5). Apart from the control group, other groups were induced by using the method of intratracheal instillation of bleomycin(5 mg/kg), the control group was treated by intratracheal instillation of saline(1.25 mL/kg)to obtain the negative control. Mice in GBE group were administered with GBE solution by gavage[0.6 g/ (kg·d)]daily; mice in GBE-NOTCH1-shRNA group were administered by tail vein injection NOTCH1 - shRNA plasmids(3 mL/kg). On the day of 28th all mice were sacrificed and observed expression and FIZZ1, NOTCH1 and α-SMA in lung tissue by RT-PCR and Western blotting. Results The severity of pulmonary fibrosis was the heaviest in model group and negative plasmids group. The severity of pulmonary fibrosis in GBE group was significantly reduced compared with model group. The severity of pulmonary fibrosis and alveolar inflammation in GBE-NOTCH1-shRNA group increased compared with GBE group. Western blotting showed the expression of FIZZ1, NOTCH1 and α-SMA in the model group was significantly higher than the control group(P<0.05). The expression of NOTCH1 and α-SMA in GBE group was significantly reduced compared with the model group(P<0.05). α-SMA protein levels in GBE-NOTCH1-shRNA increased compared with GBE group(P<0.05). The result of RT-PCR was similar to that of Western blotting. Conclusion The NOTCH signaling pathway is involved in fibroblast transit process. GBE relieves pulmonary fibrosis by inhibiting the activation of NOTCH signaling pathway.
|
Received: 30 May 2016
|
|
|
|