Mechanisms underlying the radioprotective effect of histamine on small intestine
Mechanisms underlying the radioprotective effect of histamine on small intestine
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DOI：
10.1080/09553000701570238
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Rivera, Elena S.
中科院分区：
文献类型：
--
作者：
Medina, Vanina A.;Croci, Maximo;Rivera, Elena S.
目的：探讨组胺对γ射线所致肠损伤的保护作用。材料与方法：56只小鼠随机分为4组。组胺和组胺-10戈伊组在照射前20小时开始接受每日皮下组胺注射（0.1 mg/ kg），并持续至实验期结束;未处理组接受生理盐水。组胺组和未处理组分别给予10戈伊和10戈伊剂量的铯137放射源（7戈伊/min），照射后3天处死动物。取出小肠，固定并用苏木精和伊红染色。评价了每周长肠隐窝的数量和肠细胞的其他组织学特征。我们进一步通过免疫组织化学方法测定了增殖细胞核抗原（PCNA）、Bax、Bcl-2（分别为促凋亡蛋白和抗凋亡蛋白）、抗氧化酶（超氧化物歧化酶（SOD）、过氧化氢酶和谷胱甘肽过氧化物酶）的表达、组胺含量以及通过末端脱氧核苷转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记（TUNEL）法测定细胞凋亡。通过免疫组化检测5-溴-20-脱氧尿苷（BrdU）掺入，鉴定细胞处于细胞周期的S期。结果如下：组胺处理减少了辐射暴露后小肠的粘膜萎缩、水肿和保留的绒毛、隐窝以及细胞核和细胞质特征。组胺处理后，照射小鼠脑组织PCNA表达增加，BrdU阳性细胞数增加，组胺含量增加，凋亡细胞数减少，过氧化氢酶和铜锌超氧化物歧化酶活性显著升高。结论：组胺通过增加受损肠粘膜的增殖和抑制与SOD和过氧化氢酶水平增加相关的细胞凋亡来防止辐射诱导的毒性。这种效应可能在接受放疗的患者中具有临床价值。
Purpose: To examine the protective effects of histamine on intestinal damage produced by gamma-radiation. Materials and methods: 56 mice were divided into 4 groups. Histamine and Histamine-10 Gy groups received a daily subcutaneous histamine injection (0.1 mg/ kg) starting 20 hours before irradiation and continued until the end of the experimental period; the untreated group received saline. Histamine-10 Gy and untreated-10 Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Small intestine was removed, fixed and stained with hematoxylin and eosin. The number of intestinal crypts per circumference, and other histological characteristics of intestinal cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA), Bax, Bcl-2 (pro- and anti-apoptotic protein, respectively), antioxidant enzymes ( Superoxide dismutase ( SOD), Catalase and Glutathione peroxidase), histamine content and apoptosis by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling ( TUNEL) assay. Cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-20- deoxyuridine (BrdU) incorporation. Results: Histamine treatment reduced mucosal atrophy, edema and preserved villi, crypts and nuclear and cytoplasmic characteristics of small intestine after radiation exposure. Additionally, histamine treatment increased PCNA expression and the BrdU-positive cell number, histamine content, decreased the number of apoptotic cells and significantly increased Catalase and copper-zinc-containing SOD of irradiated mice. Conclusions: Histamine prevents radiation-induced toxicity by increasing proliferation of damaged intestinal mucosa and suppressing apoptosis that was associated with an increase in SOD and Catalase levels. This effect might be of clinical value in patients undergoing radiotherapy.