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Maidong On The Prevention And Treatment Of Radiation Pneumonitis In Mice C57BL/6

Posted on:2015-05-21Degree:MasterType:Thesis
Country:ChinaCandidate:X Y WangFull Text:PDF
GTID:2284330422487580Subject:Oncology
Abstract/Summary:PDF Full Text Request
[Object] Radiation pneumonia is one of the most serious complications afterradiotherapy of thoracic tumor, present understanding of its etiology andpathogenesis is still not very clear, western clinical routinely use adrenalcortical hormone for treatment, but the side effects can not be ignored, so theprevention and control of radiation pneumonia is still an urgent problem. Wefirstly establish the mice model of radiation pneumonia, then use the singleagent Maidong extract as essential prescription, to assess its prevention andcontrol effect of radiation pneumonia, and to explore its possible mechanismby observing the level of plasma proinflammatory cytokines IL-6, TNF-αandpromote-fibrosis cytokines TGF-β1; the lung tissue hydroxyproline content,SOD activity and MDA content; the pathological morphological side effects ofthe lung tissue, and the expression of MMP-2and TIMP-2proteins.[method]60C57BL/6mice were randomly divided into four groups accordingto random number table method:(1) blank control group,(2)merely irradiatedgroup,(3)Chinese medicine (Maidong) group, and (4)western medicine(dexamethasone combine cefalexin)group, each group of15mice. Maidongextract was given1times per day to the mice of Chinese medicine group,dexamethasone and cefalexin were given1times per day to the mice ofwestern medicine group by intragastric administration from4days prior to theirradiation day, last for2weeks; merely irradiated group and blank controlgroup were given physiological saline instead.In addition to the blank controlgroup, other groups were given chest a6MV-X-ray single-wide irradiation of18Gy.Each group randomly sacrificed5mice at24hours,4weeks,12weeksafter irradiation. Took the blood of the mice after anesthesia, to detect the levelof plasma IL-6, TNF-α and TGF-β1content. Prepare left lungs intohomogenate, use alkaline hydrolysis to detect hydroxyproline content, usexanthine oxidase method to detect SOD activity, and use glucosinolatesbarbituric acid colorimetric method to detect MDA content. Fixed right lungs in formaldehyde solution, paraffin embeded,5μm serially section, observepathological changes after HE staining, detect the expression of MMP-2andTIMP-2proteins by using enzyme immunohistochemistry technique.[Results]1,compared to the blank control group,merely irradiated group①the level ofplasma IL-6, TNF-α and TGF-β1in the merely irradiated group mice weresignificantly increased (P<0.01);②hydroxyproline and MDA content of thelung tissue were significantly increased (P <0.05), SOD activity wassignificantly reduced (P <0.01);③acute inflammation changes of lung wereperformed after HE dyeing;④HIC showed significantly increase in theexpression of MMP-2and TIMP-2proteins (P <0.01), MMP-2/TIMP-2ratioincreased.It can be inferred that, given chest a6MV-X-ray single-wide irradiation of18Gy can successfully establish a radiation pneumonia model in mice withinshort time to, which will also develop into fibrosis in the future.2、①compared to the merely irradiated group, the level of plasma IL-6(P<0.01),TNF-α(P<0.05)and TGF-β1(P<0.01), hydroxyproline(P<0.05) and MDA(P<0.01)content of the lung tissue in the Chinese medicine group mice weresignificantly reduced, SOD activity was significantly enhanced (P<0.01),andthe expression of MMP-2(P<0.01) and TIMP-2(P<0.05) proteins weresignificantly reduced②compared to the merely irradiated group, the level of plasma IL-6(P<0.01),TGF-β1(P<0.01),4week hydroxyproline(P<0.05) and4week MDA(P<0.01)content of the lung tissue in the western medicine group mice weresignificantly reduced, SOD activity was significantly enhanced (P<0.01),andthe expression of MMP-2(P<0.01) and TIMP-2(P<0.05) proteins weresignificantly reduced, but the level of plasma TNF-α,12week hydroxyprolineand12week MDAcontent of the lung tissue didn’t reduce significantlycompared to merely irradiated group(P>0.05)。It can be inferred that, Maidong can inhibit or reduce the radiation pneumonia alveolar inflammatory reaction, and delay the progression ofpulmonary fibrosis, as well as dexamethasone combine cefalexin.3、 compared to the western medicine group, the level of plasma IL-6,hydroxyproline content and SOD activity of the lung tissue, the expression ofTIMP-2protein didn’t show significant difference(p>0.05); because of theincrease of the level of plasma TNF-α and TGF-β1(P<0.05), MDA(P<0.01)content of the lung tissue in western medicine group mice,theChinese medicine group were significantly different at12week; the expressionof MMP-2(P<0.05) protein the Chinese medicine group were significantlyhigher than western medicine group at4week, but didn’t show significantdifference at12week.It can be inferred that, the effect of Maidong in reducing the radiationpneumonia and delay the procession of pulmonary fibrosis is similar todexamethasone combine cefalexin, even showed a more enduring effect, andno side effects was found.[Conclusion] Maidong has certain effect on the prevention and control ofradiation pneumonia, the preventive effect may be achieved through thefollowing approaches: reduce the level of plasma proinflammatory cytokinesIL-6, TNF-αand promote-fibrosis cytokines TGF-β1; decrease the lung tissuehydroxyproline and MDA content, keep SOD activity; lessen the expression ofMMP-2and TIMP-2proteins of the lung tissue, adjust the balance ofMMP-2/TIMP-2. Maidong protect the lung effectively by multiple ways, inhibitor reduce the radiation pneumonia alveolar inflammatory reaction, and delaythe progression of pulmonary fibrosis, which is relatively more enduring thandexamethasone combine cefalexin, and no side effects was found.
Keywords/Search Tags:Maidong, radiation pneumonia, C57BL/6mice
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