The Basic Research Of Chloral Hydrate On Pulmonary Fibrosis Induced By Bleomycin In Rats

In recent years, the incidence of pulmonary fibrosis increases continuously,but the treatments to pulmonary fibrosis is limited. The topic of our study isobserving the effect of chloral hydrate to serum index and pathology of lungtissue in pulmonary fibrosis rat induced by bleomycin (BLM), and trying tolook for a new anti fibrosis drug.Objective：To observe the treatment effect of chloral hydrate to idiopathicpulmonary fibrosis (IPF) rats, comparing with dexamethasone. And to foundthe the theory basis of application of chloral hydrate to IPF.Methods：75healthy female Wistar rats were randomly divided into sixgroups: the positive control group (Group P, n=15), the Negative controlgroup (Group N, n=15), the dexamethasone treatment group (GroupD, n=15),the Chloral hydrate treatment group (Group C, n=15), the combination ofdexamethasone and Chloral hydrate group (Group C+D, n=15). Rats inNegative control group、dexamethasone group、Chloral hydrate group、thedexamethasone and Chloral hydrate group were injected with BLM (5mg/kg)through tracheofistulization to induce pulmonary fibrosis, while rats in thecontrol group were injected with equivalent physiological saline. Afteroperation, deamethasone (0.5mg/(kg.d)) was intraperitioneally subjected to thedeamethasone group rats once per day; Chloral hydrate (50mg/(kg.d)) wasintraperitioneally subjected to the Chloral hydrate group rats once per day;deamethasone (0.5mg/(kg.d)) and Chloral hydrate (50mg/(kg.d))wasintraperitioneally subjected to the combination group rats once per day.Equivalent saline was administered to rats in both the positive control groupand the Negative control group. On the7th,21th and28th day, five rats in the every group were dissected to observe the pathological changes in lung tissue.And then the concentration of TGF-βand TNF-α in the serum were determinedby enzyme-linked immunosorbent assay. Because of28rats death in theexperimental process,28additive Wistar rats were again enrolled.Results：Histopathological examination results in rat s were consistentwith the characteristics of pulmonary fibrosis. The lung ultra-strures of theNegative control group、the dexamethasone group, the chloral hydrate group,the combination group significantly changed compared with the positivecontrol group. On different time point, concentrations of TGF-β and TNF-α inserum were increased and then decreased in the Negative control group、thedexamethasone group、the chloral hydrate group、the combination group, andwere significantly higher than those of the positive control group, especially onthe7th day.TNF-α production：compared with P group, the TNF-α productionincreased (P <0.01or P <0.05) in other four groups; compared with N group,TNF-α production are lower (P <0.01) in rats of D and C+D groups;compared with group D, the change of TNF-α production is not significant inC.TGF-β production：compared with P group, TGF-β production increasedsignificantly (P <0.01) in other four groups; TGF-β production in group N wassimilar to in group D (p﹥0.05). On the7thday，there were no significantdifference in TGF-β production between group C、group C+D and group M (p﹥0.05)，but on the21thday，TGF-β production in group C、group C+D waslower than group N significantly (P <0.05), and also lower than group D (P <0.01；P <0.05).Conclusions：(1) Chloral hydrate can improve lung fibrosis to a certain extent, reduce TGF-β production in IPF rats. Otherwise, chloral hydrate can improve thesurvival rates of IPF rats, but can not reduce alveolar inflammation of IPF rats.（2）Combination of chloral hydrate and dexamethasone treatment canimprove the alveolar inflammation and reduce the degree of fibrosis,TNF-αproduction, and TGF-βprodution significantly in IPF rat. Thecombination treatment was more effective than dexamethasone single-agenttherapy.