The Pre-clinical Studies Of Yangyinqingfei Drugs On Radiation-induced Lung Injury

Objective: Based on observing the pathological signs and the expression of MMP-12and TIMP-1for radiation-induced lung injury of rat in the model,to evaluate thetreatment effect and dose-effect relationships of different doses of the YangyinqingfeiDrugs on Radiation-induced Lung Injury of rat,and to explore clinical use for the drugfurther theoretical and experimental basis.Methods:75wistar male rats were randomly divided into blank control group(Agroup), model group(B group), low dose treatment group(C group),middle dosetreatment group(D group) and high dose treatment group(E group). The rats in A groupreceived sham irradiation;others were irradiated with a single dose of25Gy to theirright hemi thoraxes by a60Coγ-ray. The rats in A and B groups were given saline aweek before irradiation,while rats in C~E groups were given different dose ofYangyinqingfei Drugs at the same time. All drugs were administered by intragastricadministration once a day. At the time of1w,2w and4w after irradiation, the effects ofdrugs were evaluated according to pathological changes, the right lung index,the levelsof MMP-12and TIMP-1from the lung homogenate.Results:1.During the whole experiment, group A presented a good spirit, activity, foodintake, and stool had no obvious abnormality.Compared with group A, group Bpresented a symptom of less eating,loss weight, less activities,dry stool,redness of thenose, withered fur off, and skin erosion, ulcer.Compared with group B, the symptoms inC~E groups were alleviated, and had no skin erosions, ulcers.Between C~E groups, thesymptoms in the group D was mildest, and the group E rats presented stool smelly.2.The surface of right lung in the group A was smooth, pink, shiny, and good elasticity;In the first week, the surface of right lung in the group B presented dark red,nosignificant changed in gross morphology. In the2nd week,the surface of right lung wasswelling than left;4weeks after the irradiation the right lung surface presented petechiae, visible white nodule-like, and pleural effusion. The C~E groups had lesslesions than the group B.3. To observe the lung beneath a microscope, the group A lung structure was normal,the alveolar wall was thinner, the alveolar spaces without exudation and effusion.In thefirst week after irradiation, the alveolar wall of group B presented mild edema,capillary congestion, alveolar space showed a small amount of exudation andinflammatory cell infiltration, interval without obvious exudation, congestion andedema. In the2nd week after irradiation alveolar septa was significantly thicker andmore pronounced inflammatory cell invasion, part of the alveolar structuredisappeared.In the4th week after irradiation perivascular inflammatory cells, interstitiallung congestion, the accumulation of macrophages, lymphocytes, alveolar wallthickening were observed, alveolar space significantly collapsed or even disappeared,part of the alveolar space to expand compensatory, the formation of emphysemasymptoms, visible fiber cell hyperplasia, focal fibrosis. During the whole experiment,the pathological changes in the C~E groups are milder than group B.4. The expression of the lung tissue of MMP-12and TIMP-1increased afterirradiation.The expression of MMP-12in group B was up-regulated and reached thepeak at the2nd week.From the4th week the expression reduced markedly. Theexpression of TIMP-1continues to rise.Compared with those in the group B,the levelsof MMP-12and TIMP-1in groups C~E were lower.Conclusion:1. Yangyinqingfei Drugs can lessen the inflammation of the lung tissueand interstitial fibroblast proliferation after irradiation, and has a significant role infight against early radiation-induced lung injury.2. Yangyinqingfei Drugs can early prevent the expression of MMP-12、TIMP-1in theradiation-induced lung injury.3.Yangyinqingfei Drugs has the effect of prevention and treatment on the earlyradiation-induced lung injury.Middle-dose and high-dose group were better thansmall-dose, however there’s no difference between them. Suggest that Middle-dose is the most effective. If the doses of drugs were aggrandized, it would not enhance theeffects of prevention and cure for radiation-induced lung injury but other side effect,such as diarrhea.