| Objective：pumlonary interstitial fibrosis is a kind of unknown etiologydiffuse lung disease With the characteristics of inflammatory reaction intofiber cell proliferation and extracellular matrix deposits。 It has manycomplicated pathogenesis and is offen attacked after age50。Lung functiondisplay restrictive ventilation function obstacle and severe dispersion functionobstacle.Blood gas analysis shows serious hypoxia. The disease prognosis isbad and Most of the patients died of respiratory failure. Its pathogenesisunclear, and there is no specific treatment measures. The treatment method ismainly to use of corticosteroids or joint immunosuppressive agents. But thetreatment is not ideal, and is toxicity. The new treatment concept, methodsand drug is extremely important. Lung fibroblasts in vitro studies researchshows that prostaglandin E2can restrain fibroblasts value-added and collagensynthesis,and the infection of TNF to fibrosis is negative.This experiment was designed to use sailaixibu to suppress theprostaglandin synthesis of the rats who are induced pulmonary fibrosis bybleomycin. Through observing distribution of zhe prostaglandin in zhe lungtissue and Measuring expression level of the CAMP TNF in the lunghomogenate,to Observae the changes of prostaglandin E2and discuss thesignificance and mechanism.At zhe same time,giving dmPGE2intervention,tofurther demonstratde the function and mechanism of PGE2in pulmonaryfibrosis drug.Method:90healthy male Sprague-Dawley(SD) rats(provided by CenterExperiment Animal of Hebei Medical University) weighting220±10g wererandomly divided into three groups after one week feeding.1) Control group(group A):30rats. They were injected about normal saline (0.1ml/100g) intrachea, and were given intragastric administration with normal saline once a time per day, at the same time they were also given intramuscular injectionof with normal saline once a time per day after establishing model, thenwere killed randomly on the7thday, the14thday and the28thday (n=10, ateach time point).2) Model group (group BLM):30rats. Pumlonary fibrosiswas induced by intratracheal injection of Bleomycin (5mg/kg),and weregiven intragastric administration with normal saline once a time per day, atthe same time they were also given intramuscular injection of with normalsaline once a time per day after establishing model, then were killedrandomly on the7thday (n=8), the14thday (n=9) and the28thday (n=8).3)Sailaixibu group (group SL):30rats. They were injected Bleomycin(5mg/kg) in trachea, and they were treated with Sailaixibu solution250mg/kgonce a time per day from zhe seventh day after establishing model, beforethis, at the same time they were also given intramuscular injection of withnormal saline once a time per day after establishing model, then were killedrandomly on the7thday(n=8), the14thday(n=8) and the28thday(n=6), GroupdmPGE2(group PG) they were given intramuscular injection with normalsaline (100ug/kg.d) once a time per day after establishing model. Useingsaline instead of Sailaixibu, and were given intragastric administration withnormal saline once a time per day, Then they were killed randomly on the7thday(n=9), the14thday(n=10) and the28thday(n=9)at each time point).Therats were Bleed to death before taking the BALF and lung tissues.The content of TNF-α and CAMP in BALF were detected. The inferiorlobes of right lung were fixed in4%paraformaldehyde. The levels of PGE2was measured by immunohistochemical test, and positive area percentage ofthem were determined by sem quantitative picture analysis. Estimate thedegree of alveolitis and pulmonary fibrosis by HE staining, Masson stainingand divide by the method of Szapiel into4grades.The superior lobes of rightlung were made into homogenate to evaluate the concentration of HYP in lungtissue. Statistics work was done with SPSS13.0statistical software.Results：1The results of pulmonary pathology: The level of alveolitis of group BLM was more serious than that in group NS at each time point(P<0.05). The levelof fibrosis in group BLM was also more serious than that in group NS on theeach time point day(P<0.05). These indicate that the model of pulmonaryfibrosis estabished successfully. The levels of fibrosis in group SL weremore serious than that in group BLM on the28thday.But there was notobvious diffience between the groups BLM and SL with the leve of alveolitis.The levels of alveolitis and fibrosis in group PG were less serious than that ingroup BLM at each time point(p<0.05).2The change of the content of HYP in lung tissue: The content of HYP ingroup BLM shown an increase tendency accompany with the time andreached a peak on the28thday. Compared with group NS, there weresignificant difference on each time point (P<0.05). The values of HYP of therats in group SL were also increased with a higher level than the group ofBLM. The content of HYP in group PG were all higher than that in group NSon the7thday, the14thday and the28thday(P<0.05),but it was lower than thegroup of BLM at each point time.3The change of the content of PGE2in lung tissue: The expression of PGE2in group BLM was higher than that in group of NS a on the7th day, but on the14thand28thday,the expresson of group BLM was lower than the group NS.Certenly the expression of PGE2in group SL were lower than that in group ofBLM on the14thand28thday. the expression of PGE2in group PG werehigher than that in group of BLM on the14thand28thday.4The change of the content of TNF-α and CAMP in BALF: The content ofTNF-α in group BLM was significantly higher than that in group NS on eachtime point (P<0.05), but the content of CAMP in the group BLMwassignificantly lower than that in group NS on the14thand28thday(P<0.05).Between the group SL and BLM,the content of TNF-α in group SLwas increased,the CAMP was indecread.But Compared with the groupBLM,the content of TNF and CAMP in group PG have opposite changes.Conclusions:1Making pulmonary fibrosis model was successful through the endotracheal drip into the bleomycin, Can appear alveolar inflammation andpulmonary fibrosis.2The PGE2in the lung tissue of rats who han the disease of IPF was lowerthan the Healthy rats,especialy in the later stage of fibration.In the BALF,thecontent ofTNF Was increased,the conten of CAMP Was indecreasef.3If inhibiting the synthesis of the PGE2in the later alveolar inflammation,weifind that the content of HYP in the lung tissue and The extent of fibrosis wasincread. This Suggests that PGE2can restrain fiberize of the lung thoughdecreasing the content of TNF and increasing the content of CAMP.4There was no obvious difference between the group BLM and the group SLwith alveolar inflammation, but if inhibiting the PGE2synthesis can makepulmonary fibrosis aggravating. This suggests that the deterioration of thepulmonary fibrosis can not be closed to the inflammation.5Using of dmPGE2can reduce the reduce the degree of the alveolarinflammation and the idiopathic pulmonary fibrosis. |
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