Shashen Maidong Decoction On The Prevention And Treatment Of Radiation Pneumonitis In Rats And Its Mechanism

ObjectiveThe incidence of radiation pneumonitis was a rising trend year by year,present their understanding of the etiology and pathogenesis is not very clear,western clinical routine use for treatment of adrenal cortical hormone, but the side effects, so the prevention of radiation pneumonitis is an urgent solution problems. Large number of clinical studies have shown that prevention and treatment of chinese medicine is effective, can improve clinical symptoms, improve quality of life, reduce mortality, prevention and treatment of radiation pneumonitis in medicine has very important practical significance.Shashen(沙参)Maidong(麦冬)Decoction is clinically effective prescription prevention and treatment of radiation pneumonitis, and is one of the traditional ancient prescriptions of traditional Chinese medicine, Shashen Maidong Decoction has not yet found the mechanism of prevention and treatment of radiation pneumonitis reported. First copy the rat model of radiation pneumonitis, to proinflammatory cytokines and cytokines promoting fibrosis as the starting point, the foundation from the syndrome of radiation pneumonitis (lung yin deficiency). Shashen Maidong Decoction to the Basic prescription, to observe the pathological side effects of lung tissue; of the lung tissue SOD activity, MDA content; of matrix metalloproteinase (MMP-2) and tissue inhibitor (TIMP-2) protein expression effects; especially proinflammatory cytokines TNF-α, IL-6 and promote f ibrosis cytokine TGF-β1 impact study to assess Shashen Maidong Decoction on the control effect of radiation pneumonitis, and to explore its possible Mechanism for clinical use to provide hard scientific basis.MethodsThe 141 male SD rats of clean grade were randomly divided into normal control group, model group, Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group,21 rats of normal control group, the other each group were 30. In addition to the normal control group, other groups were given chest X-ray single-wide exposure 20Gy. Apart from Shashen Maidong Decoction prevention group started 1 week before radiation fed Shashen Maidong Decoction, the rest of the group the next clay after modeling, the normal control group, model group were given the same volume of normal saline, Shashen Maidong Decoction treatment group fed Shashen Maidong Decoction, dexamethasone treatment group were given dexamethasone suspension once a day. Each group were sacrificed at 2,4,6 weeks,7 rats in normal control group,10 rats in other groups.10% solution of chloral hydrate anesthetized rats by intraperitoneal injection, heart blood about 5ml, centrifuged (2000r/min×10min) after the specimens from the supernatant,-20℃tested under storage; collected lung tissue of rats, weighing, calculating changes in lung coefficient; HE Stained pathological changes of lung tissue; observed by immunohistochemistry in lung tissue MMP-2, TIMP-2 protein expression; ELISA assay of plasma IL-6, TNF-α, TGF-β1 content; chemical assay for measuring lung tissue MDA, SOD content changes; by reverse transcription polymerase chain reaction (RT-PCR) method of lung tissue expression of MMP-2mRNA changes.Results(1) Shashen Maidong Decoction could significantly reduce the coefficient of rat lung radiation pneumonitis (p<0.01), Shashen Maidong Decoction prevention group was superior to Shashen Maidong Decoction treatment group, Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group differences between groups were statistically different (P<0.05); lung pathology observations showed that Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group compared with model group, inflammatory cell infiltration, alveolar congestion, exudation, bleeding and so to a lesser extent. Inflammation from heavy to light as follows:model group and dexamethasone treatment group, Shashen Maidong Decoction treatment group, Shashen Maidong Decoction prevention group. Dexamethasone treatment group in which a small abscess occurs, consideration is caused by decreased immunity of. dexamethasone, concurrent infection. Normal lung tissue structure is clear, bronchial, alveolar and organizational structure of the normal alveolar septa, no alveolar septal infiltration of neutrophils, no congestion, edema and acute and chronic inflammation changes. Each time point were not significant pathological changes.(2)Compared with the control group, model, group SOD activity in lung tissue were decreased (P<0.01), MDA content increased (p<0.05); compared with the model group, Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group in lung tissue SOD activities increased (P<0.01), MDA content decreased (P<0.01). SOD activity in order were:Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group, model group (P<0.01). Shashen Maidong Decoction prevention group than the Shashen Maidong Decoction treatment group (P<0.01). Shashen Maidong Decoction treatment group than the dexamethasone treatment group (P<0.05).(3)Compared with the control group, model group, plasma IL-6, TNF-α, TGF-β1 content of value in the first week were significantly higher 2,4,6 (P<0.01). Compared with model group, Shashen Maidong Decoction prevention group, Shashen Maidong Decoction treatment group, dexamethasone treatment group, plasma IL-6, TNF-α5, TGF-β1 was significantly lower (P<0.01 or p<0.05). Shashen Maidong Decoction prevention group than Shashen Maidong Decoction treatment group (P<0.01), Shashen Maidong Decoction treatment group than the dexamethasone treatment group (p<0.01).(4) with the normal control group,2 to 4 weeks, MMP-2, TIMP-2 protein in model group rats lung tissue were increased (p<0.01), but MMP-2/TIMP-2 ratio increased. After 4 weeks, MMP-2 protein in rats lung tissue decreased and gradually increased the, expression of TIMP-2, MMP-2/TIMP-2 ratio became smaller. Compared with model group, MMP-2, TIMP-2 protein expression in Shashen Maidong Decoction prevention group and treatment group was significantly lower (P<0.01 or p<0.05), MMP-2/TIMP-2 at a relatively Equilibrium. Dexamethasone treatment group at each time point MMP-2, TIMP-2 compared with the model changes, no significant difference (P>0.05). Shashen Maidong Decoction prevention group compared with Shashen Maidong Decoction treatment group:2,4 weeks were significantly different (P<0.05),6 weeks without significant difference (P>0.05). Shashen Maidong Decoction treatment group compared with the dexamethasone treatment group:2,4 weeks, no significant difference (P>0.05),6 weeks significant difference (P<0.05).(5)Compared with the control group, lung tissue expression levels of MMP-2mRNA in model group-increased (P<0.01); compared with model group, lung tissue expression of MMP-2mRNA in treatment groups significantly reduced(P<0.01). compared with Shashen Maidong Decoction treatment group, Shashen Maidong Decoction prevention group has no significant difference (P>0.05); Shashen Maidong Decoction treatment group compared with the dexamethasone treatment group:2,6 weeks (P<0.01),4 weeks (P<0.05).ConclusionShashen Maidong Decoction on the prevention and treatment of radiation pneumonitis have a certain effect. The preventive effect may be achieved through the following channels:enhanced activity of SOD in lung tissue and reduce the MDA content; suppressed plasma levels of inflammatory cytokines IL-6, TNF-αpromoter and promote fibrosis, TGF-β1 cytokine release; reduce radiation pneumonitis Rat lung tissue MMP-2, TIMP-2 protein expression, regulating the balance of MMP-2/TIMP-2; reduce radiation pneumonitis in lung tissue of MMP-2 mRNA expression. Effective protection from lung tissue various channels, to varying degrees, inhibit or reduce the alveolar inflammatory response, and can inhibit the process of pulmonary fibrosis, and prevention better than cure, prevention is better than dexamethasone, did not find any side effects.