| Pulmonary fibrosis(PF)is a multi-caused diffuse lung disease,which caused by repeated stimulation of multiple pathogenic factors and represented with a great deal of Fibroblast(FB)'s morbid multiplication,extracellular matrix(ECM)'s exceptional accumulation and replace of normal lung tissue systemic.The mechanism of PF has not been fully understood,which is related with oxygenation,hyperirritability,inflammation,unbalance of the cell gene and activation of special signal pathway.There is lack of effective and secure drug.The epidemiology investigation reveals the ascending trend of the annual incidence and death rate.The impendence is to indagate the mechanism and find effective and secure drugs.5,7,3'-triacetyl hesperidin(5,7,3'-triacetyl hesperidin,TAHP),is a structure modified derivatives of hesperidin((hesperidin,HDN)),which retains the hesperidin's anti-oxidation,anti-inflammatory,analgesic and immunomodulatory pharmacological properties on the basis of solving the disadvantage of low solubility and bioavailability of hesperidin,which is a flavanone glycoside synthesized from the hesperidin and the disacchatide rutinose.Research proves that 5,7,3'-triacetyl hesperidin has strong anti-inflammatory analgesic,immunity and anti-oxidation function,although its mechanism is unclear,but the type of adjuvant arthritis,liver fibrosis and other animal experimental model has achieved a certain degree of curative effect,at present,5,7,3'-triacetyl hesperidin in pulmonary fibrosis effect needs further research.Stem cell factor(stem cell factor,SCF)depend on the specifical receptor(C-kit receptor,CD117)to play its role,which form polymer,and activate the corresponding signal pathway.SCF/ C-kit promote cell proliferation,differentiation,movement,invasion,energy metabolism,apoptosis and other biological effects.Early studies confirmed that the ERK signaling pathway,the JAK-STAT pathway associated with pulmonary fibrosis,All of which are the downstream signal transduction pathways activated by the SCF/c-kit pathway.There is no research about the relationship between SCF/c-kit pathway and pulmonary fibrosis.The study showed the relationship with SCF/c-kit signal pathway and cell's abnormal multiplication.However,this provides a theoretical basis for the study of SCF/c-kit pathway in pulmonary fibrosis..The pulmonary fibrosis model was established by intra-tracheal injection of Bleomycin A5(5mg/kg)on rats,in order to observe the therapical effects of 5,7,3'-triacetyl hesperidin to PF and the relationship with SCF/c-kit signal pathway.Rats were treated with 5,7,3'-triacetyl hesperidin(50,100,200 mg/kg)and dexamethasone(1.4 mg/kg)by intragastric administration.Random sampling was taken on seventh,fourteenth and twenty-eighth day.The pathomorphology in lung tissue were analyzed.Malonaldehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)and hydroxyproline(HYP)in lung tissue were studied.The effects of 5,7,3'-triacetyl hesperidin on the expressions of stem cell factor(SCF),receptor c-Kit,transforming growth factor-?1(TGF-?1)and alpha-smooth muscle actin(?-SMA)in lung tissue of rats were assayed by RT-PCR.TGF-?1??-SMA expression was evaluated by western blot.The study indicated: 1.5,7,3'-triacetyl hesperidin could obviously reduce alveolitis and pulmonary fibrosis.5,7,3'-triacetyl hesperidin reduce the contents of MDA and HYP and enhance the level of GSH and SOD in lung tissue.It also inhibited m RNA expression of TGF-?1,?-SMA in lung tissue of PF rats.These results suggest that5,7,3'-triacetyl hesperidin has therapeutic effects of Bleomycin A5-induced pulmonaryfibrosis rats in a dose-dependent manner,which might be related with the anti-oxidation and inhibition of TGF-?1.2.SCF and c-Kit's m RNA expression of Model group was obviously higher than blank group,the change of which was the negative correlation to medicine dose,tip: the PF process probably activate the SCF/c-Kit signal pathway,the effect of 5,7,3'-triacetyl hesperidin against PF may be related to the regulation of SCF/c-Kit signal pathway. |
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