| Objective: Interstitial lung disease(ILD) includes a large group of pulmonary diffuse diseases. The main pathological changes are not only pulmonary interstitial in anatomy, but also lung parenchyma, such as alveolar epithelial cell, vascular endothelial cell and so on. The main pathological changes happen in alveolar wall, as well as bronchiole. At present, some scholars think that diffuse parenchymal lung disease(DPLD) is more appropriate. Bleomycin(BLM) is a kind of anti-tumor drugs. It is widespreadly applied to gynecological tumor, lymphoma etc. About 10-30 percent of patients who used BLM develop lung toxicity, with clinical manifestations of dyspnea, cough, chest pain and lung rales etc, which result in non-specificity pneumonia and pulmonary fibrosis, even dying of pulmonary fibrosis immediately. The imbalance of oxidative and anti-oxidative may be important in the process of the disease. The main purpose of the experiment is to observe the effects of reduced glutathione(GSH) on belomycin-induced pulmonary fibrosis in rats and to compare with the traditional drug hormone(H),detecting the contents of hyaluronan(HA) and typeⅢprocollagen(PCⅢ) in blood serum and the expression level of tumour necrosis factor-α(TNF-α) in lung tissue.Methods:90 healthy male Sprague-Dawley(SD) rats (provided by Center Experiment Animal of Hebei Medical University), weighting about (250±10 g),were randomly divided into five groups after one week feeding. (1)Normal control group(group N): 18 rats, They were injected about normal saline (0.1ml/kg) in trachea, and treated with normal saline (0.2ml/100g) intraperito- neally once a time per day after fake establishing model, then were killed randomly on the 7th day, the 14th day and the 28th day (6 rats, on each time point).(2)Bleomycin model group(group A):18 rats. Pulmonary fibrosis was induced by intratracheal injection of Bleomycin A5 (5mg/kg).They were injected normal saline intraperitoneally once a time per day after establishing model, then were killed randomly on the 7th day, the 14th day and the 28th day(6 rats, on each time point).(3)Hormone group(group B): 18 rats. They were injected Bleomycin A5 (5mg/kg) in trachea, and treated with Dexame- thasone(0.5mg/kg) intraperitoneally once a time per day after establishing model, then were killed randomly on the 7th day, the 14th day and the 28th day(6 rats, on each time point).(4)GSH low dose group(group C): 18 rats. They were injected Bleomycin A5 (5mg/kg) in trachea, and treated with GSH(0.1g/kg) intraperitoneally once a time per day after establishing model, then were killed randomly on the 7th day, the 14th day and the 28th day(6 rats, on each time point).(5)GSH high dose group(group D): 18 rats. They were injected Bleomycin A5 (5mg/kg) in trachea, and treated with GSH(0.4g/kg) intraperitoneally once a time per day after establishing model, then were killed randomly on the 7th day, the 14th day and the 28th day(6 rats, on each time point).The rats were killed by snipping ventral artery and vein for collecting the blood. The levels of HA and PCIII in serum were observed with radio-immunoassay. The right middle lung(R.M.L) was preserved in 10% formalin for tissue fixation after breaking lobe of the right. Then the level of TNF-αcan be measured by immunohistochemical method and the mean gray scale value of TNF-αcan be measured by image analytical system. HE and Masson pigmentations can be used to test the extent of alveolitis and pulmonary fibrosis, which are divided into 4 grades by the Szapiel method ("1"represents no alveolitis or pulmonary fibrosis;"4"represents severe alveolitis or pulmonary fibrosis and more than half of area is involved).Results:1 The result of pulmonary pathology: The level of alveolitis in group A was more serious than that in group N on each time point(P<0.01). The level of fibrosis in group A was more serious than that in group N on the 14th day and the 28th day(P<0.01). These indicated that the model of pulmonary fibrosis established successfully. The levels of alveolitis and fibrosis in group B and group C were less serious than that in group A.The levels of alveolitis in group B and group C were less serious than that in group A on the 7th day(P<0.01). The levels of alveolitis in group B and group C were less serious than that in group A on the 14th day(P<0.05).The levels of fibrosis in group B and group C were less serious than that in group A on the 28th day(P<0.05),but there were no significant differences between group B and group C(P>0.05).The levels of alveolitis and fibrosis in group D were less serious than that in group B, but there was no differences(P>0.05).2 The change of the content of HA in serum: The values of HA in all the other groups were significantly higher than that in group N on the 7th day, the 14th day, there were significant differences(P<0.01).Compared with group N, Group A and group B had significant differences on the 28th day(P<0.01), the GSH groups had no differences(P>0.05).Compared with group A, group B and the GSH groups had significant differences on the 7th day (P<0.01),only GSH groups had significant differences on the 14th day and the 28th day. Compared with the intervention groups, group B was significantly different from GSH groups on each time point(P<0.01), but there was no difference between GSH groups(P>0.05).3 The change of the content of PCⅢin serum: Compared with group N, the values of serum PCⅢin group A were higher on the 7th day and the 14th day, and reached a peak on the 14th day, then decreased, there were significant difference(P<0.01),on the 28th day, there were also difference(P<0.05). Compared with group A, the values of serum PCⅢin group B and GSH groups were lower on each time point after the model was established and there were significant difference(P<0.05).Compared with the intervention groups, there were no differences among group B and GSH groups(P>0.05),there were no differences between GSH groups(P>0.05).4 The expression of TNF-αin lung tissue: The expression of TNF-αin group A gradually increased following the prolong of the time, it was significantly higher than that in group N on the 7th day, the 14th day and the 28th day (P<0.01),and reached a peak on the 28th day. The expressions of TNF-αin the interventive groups had an increasing tendency with a low level and the extent of the height set down significantly. The expressions of TNF-αin the inter- ventive groups were significantly lower than that in group A on the 7th day, the 14th day and the 28th day(P<0.01).There were no differences among group B and GSH groups on each time point(P>0.05).There were no differences between GSH groups (P>0.05).The expression of TNF-αon the 7th day after the model was established, had no difference between group D and group N(P>0.05).Conclusions:1 GSH could prevent from the progression of pulmonary fibrosis, reduce the inflammation in bleomycin-induced pulmonary fibrosis, especially in the early stage.2 There was no side effect on pulmonary fibrosis in rats through intraperitone- al injecting high dose of GSH. It didn't appear hormonelike adverse reaction.3 The effect of GSH on pulmonary fibrosis in rats possibly related with its anti-oxidation, which could reduce inflammation.
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