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二羟丙茶碱对博来霉素诱导的大鼠肺纤维化的保护作用。

Protective effect of dexpanthenol on bleomycin-induced pulmonary fibrosis in rats.

机构信息

Department of Pulmonary Medicine, Inonu University Faculty of Medicine Turgut Ozal Medical Center, Elazig Yolu 15.km, 44280, Malatya, Turkey,

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2013 Dec;386(12):1103-10. doi: 10.1007/s00210-013-0908-6. Epub 2013 Aug 31.

Abstract

Despite extensive studies, there is no effective treatment currently available other than pirfenidone for idiopathic pulmonary fibrosis. A protective effect of pantothenic acid and its derivatives on cell damage produced by oxygen radicals has been reported, but it has not been tested in bleomycin (BLM)--induced pulmonary fibrosis in rats. Therefore, we aimed to investigate the preventive effect of dexpanthenol (Dxp) on pulmonary fibrosis. Thirty-two rats were assigned to four groups as follows: (1) control group, (2) dexpanthenol (Dxp) group; 500 mg/kg Dxp continued intraperitoneally for 14 days, (3) bleomycin (BLM) group; a single intratracheal injection of BLM (2.5 mg/kg body weight in 0.25-ml phosphate buffered saline), and (4) BLM + Dxp-treated group; 500 mg/kg Dxp was administered 1 h before the intratracheal BLM injection and continued for 14 days i.p. The histopathological grades of lung inflammation and collagen deposition, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and myeloperoxidase (MPO) were measured. BLM provoked inflammation and collagen deposition (p < 0.0001), with a marked increase in myeloperoxidase (MPO) activity resembling increased inflammatory activity (p < 0.0001), which was prevented by Dxp (p < 0.0001, p = 0.02). BLM reduced tissue activities of SOD, GPx, and CAT compared to controls (p = 0.01, 0.03, 0.009). MDA was increased with BLM (p = 0.003). SOD (p = 0.001) and MDA (p = 0.016) levels were improved in group 4. The CAT levels in the BLM + Dxp group were close to those in the control group (p > 0.05). We showed that Dxp significantly prevents BLM-induced lung fibrosis in rats. Further studies are required to evaluate the role of Dxp in the treatment of lung fibrosis.

摘要

尽管进行了广泛的研究,但除了吡非尼酮之外,目前对于特发性肺纤维化还没有有效的治疗方法。有报道称,泛酸及其衍生物对氧自由基引起的细胞损伤具有保护作用,但尚未在博来霉素(BLM)诱导的大鼠肺纤维化中进行过测试。因此,我们旨在研究地潘酮(Dxp)对肺纤维化的预防作用。32 只大鼠被分为四组:(1)对照组;(2)地潘酮(Dxp)组;腹腔内连续注射 500mg/kg Dxp 共 14 天;(3)博来霉素(BLM)组;气管内单次注射 BLM(2.5mg/kg 体重于 0.25ml 磷酸盐缓冲液中);(4)BLM+Dxp 治疗组;BLM 气管内注射前 1 小时腹腔内注射 500mg/kg Dxp,共 14 天。测量肺炎症和胶原沉积的组织学分级、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和髓过氧化物酶(MPO)的组织水平。BLM 引起炎症和胶原沉积(p<0.0001),髓过氧化物酶(MPO)活性显著增加,类似于炎症活性增加(p<0.0001),Dxp 可预防这种情况(p<0.0001,p=0.02)。BLM 与对照组相比,组织 SOD、GPx 和 CAT 活性降低(p=0.01,0.03,0.009)。BLM 引起 MDA 增加(p=0.003)。第 4 组 SOD(p=0.001)和 MDA(p=0.016)水平得到改善。BLM+Dxp 组的 CAT 水平接近对照组(p>0.05)。我们表明,Dxp 可显著预防博来霉素诱导的大鼠肺纤维化。需要进一步研究来评估 Dxp 在肺纤维化治疗中的作用。

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