Protective effect of orally administered carnosine on bleomycin-induced lung injury
Protective effect of orally administered carnosine on bleomycin-induced lung injury
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DOI：
10.1152/ajplung.00283.2006
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Vancheri, Carlo
中科院分区：
文献类型：
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作者：
Cuzzocrea, Salvatore;Genovese, Tiziana;Vancheri, Carlo
肌肽是由β-丙氨酸和L-组氨酸组成的内源性合成的二肽。它作为一种自由基清除剂，并具有抗氧化性能。肌肽在不同的实验环境中减少促炎症和促纤维化细胞因子，例如转化生长因子-β（TGF-β）、IL-1和TNF-α。在本研究中，我们研究了肌肽对博莱霉素诱导的肺损伤动物模型的疗效。对小鼠进行博莱霉素的腹膜内施用，并分配每天通过150 mg/kg的口服推注接受肌肽。纤维化诱导后一周，进行支气管肺泡灌洗（BAL）细胞计数和TGF-β水平、肺组织学和髓过氧化物酶、TGF-β、诱导型一氧化氮合酶、硝基酪氨酸和聚（ADP-核糖）聚合酶的免疫组织化学分析。最后，通过末端脱氧核苷酸转移酶介导的UTP末端标记法定量细胞凋亡。博莱霉素给药后，与野生型小鼠相比，肌肽处理的小鼠表现出肺损伤和炎症程度降低，如1）体重降低，2）死亡率降低，3）嗜中性粒细胞肺浸润降低所示。（髓过氧化物酶活性和BAL总细胞计数和分类细胞计数），4）肺水肿，5）肺损伤和胶原沉积的组织学证据，6）肺髓过氧化物酶、TGF-β、诱导型一氧化氮合酶、硝基酪氨酸和聚（ADP-核糖）聚合酶免疫染色，7）BAL TGF-β水平，和8）细胞凋亡。我们的研究结果表明，口服肌肽能够预防博莱霉素诱导的肺损伤，可能是通过其直接的抗氧化特性。肌肽已经可供人类使用。它可能被证明是有用的作为一个附加治疗的肺纤维化疾病的氧化应激发挥作用，如特发性肺纤维化，一种疾病，仍然是一个重大的挑战，以医学治疗。
Carnosine is an endogenously synthesized dipeptide composed of beta-alanine and L-histidine. It acts as a free radical scavenger and possesses antioxidant properties. Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-beta (TGF-beta), IL-1, and TNF-alpha in different experimental settings. In the present study, we investigated the efficacy of carnosine on the animal model of bleomycin-induced lung injury. Mice were subjected to intratracheal administration of bleomycin and were assigned to receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis induction, bronchoalveolar lavage (BAL) cell counts and TGF-beta levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-beta, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase were performed. Finally, apoptosis was quantified by terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin administration, carnosine- treated mice exhibited a reduced degree of lung damage and inflammation compared with wild-type mice, as shown by the reduction of 1) body weight, 2) mortality rate, 3) lung infiltration by neutrophils ( myeloperoxidase activity and BAL total and differential cell counts), 4) lung edema, 5) histological evidence of lung injury and collagen deposition, 6) lung myeloperoxidase, TGF-beta, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-beta levels, and 8) apoptosis. Our results indicate that orally administered carnosine is able to prevent bleomycin-induced lung injury likely through its direct antioxidant properties. Carnosine is already available for human use. It might prove useful as an add-on therapy for the treatment of fibrotic disorders of the lung where oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.