Experimental study for TianLongjie regulation on Pulmonary Fibrosis Rats by Notch sig-naling pathway
Objective To observe the effect of TianLongjie on the Notch signaling pathway of bleomycin-induced pulmonary fi-brosis in rats,and to explore the mechanism of TianLongjie on pulmonary fibrosis(PF).Methods Wistar rats were replicated by endotracheal infusion of bleomycin(Bleomycin,BLM),and then which were randomly divided into model group(Model),Tianlong low dose group(TL),Tianlong medium dose group(TM),Tianlong high dose group(TH),and positive drug pirfenidone group(PFD),except the blank group(Control),was with 10 rats in each group.A rat pulmonary fibrosis model was prepared by tra-cheal instillation of bleomycin,and after 14 days of modeling,TianLongjie was given by low,medium and high doses of intragas-tric administration(0.51 g·kg-1·d-1;1.01g·kg-1·d;2.02g·kg-1·d-1),pirfenidone was given by gavage(0.12mg·kg-1·d-),and the blank group and the model group were given the same amount of normal saline,administered once a day for 28 days.After pulmonary function tests,lung tissue is collected and weighed to calculate the lung index.Hematoxylin-eosin staining(HE)and Masson staining were used to observe the pathological changes of rat lung tissue.The expression of TGF-β,α-SMA,COL-Ⅰ,COL-Ⅲ,Hes1,DLL4,Notch1 and immunohistochemistry was detected by real-time polymerase chain re-action(real-time PCR)and Western blotting.Results Compared with the control group,the lung index of the model group was increased,and the alveolar structure was destroyed by HE and Masson staining,a large number of inflammatory cells were infiltra-ted,blue collagen fibers were deposited in the lung interstitium,and the fibrotic lesions were obvious,the mRNA and protein ex-pressions of TGF-β,α-SMA,VEGF,COL-Ⅰ,COL-Ⅲ,Hes1,DLL4 and Notch1 were up-regulated in lung tissues.Compared with the model group,the lung index of the rats in the Tianlong exhaustion intervention group decreased,and HE and Masson staining showed that the inflammatory cell infiltration,alveolar structure destruction and fibrotic lesions in lung tissue were reduced,and the mRNA and protein expressions of TGF-β,α-SMA,VEGF,COL-Ⅰ,COL-Ⅲ,Hes1,DLL4 and Notch1 were down-regulated in lung tissues.Conclusion TianLongjie can down-regulate the expression of VEGF,Hes1,DLL4 and Notch1,reduce the expression of pulmonary fibrosis indexes TGF-β and α-SMA,reduce the lung index deposition of COL-Ⅰand COL-Ⅲ collagen in lung tissue,which may be improved by regulating the Notch signaling pathway.
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