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N-乙酰半胱氨酸对大鼠小肠辐射损伤的防护作用
王瑜1△,张再重1△,陈少全1,王烈1*,郑国华2
0
(1.南京军区福州总医院普通外科,南京军区普通外科研究所,福州 350025;2.福建中医学院护理学系,福州 350000)
摘要:
目的:探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对小肠辐射损伤的防护作用及其作用机制。方法:60只雄性SD大鼠随机分为5组,单纯照射组(n=12)仅接受单次腹部照射;高、中、低剂量NAC给药组(n=12)均接受10 Gy X线单次腹部照射并分别给予腹腔注射NAC 300、200、50 mg/kg,连续7 d;正常对照组(n=12)给予腹腔注射1 ml 0.9 % NaCl溶液,连续7 d。NAC 在单次腹部照射前3 d开始经腹腔注射给药,至照射后第3日结束。照射后第3日,禁食12 h后处死大鼠,取血与末端回肠标本。光镜下观察并计算单位面积肠片上的肠腺存活率和绒毛数,测定血浆中D-乳酸含量和二胺氧化酶(diamine oxidase,DAO)活性,检测小肠组织中超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(glutathione,GSH)含量。结果:照射后大鼠末端回肠肠黏膜结构受到破坏,血浆中D-乳酸、DAO含量显著升高,小肠组织中SOD活性、GSH含量显著降低,MDA含量显著升高(P<0.01)。不同剂量NAC给药处理后可不同程度地降低小肠黏膜绒毛数减少并提高肠腺存活率(P<0.05,P<0.01),抑制血浆中D-乳酸、DAO含量升高,提高小肠组织中SOD、GSH含量并减少脂质过氧化产物MDA的生成(P<0.05,P<0.01)。结论:NAC通过增强机体抗氧化能力、减轻肠屏障功能障碍的严重程度,维护机体内氧化还原平衡以及小肠黏膜结构和功能的完整性,对小肠辐射损伤起到有效的防护作用。
关键词:  N-乙酰半胱氨酸;小肠;辐射损伤  辐射防护;放射性肠炎;肠屏障功能障碍
DOI:10.3724/SP.J.1008.2008.00651
投稿时间:2007-11-17修订日期:2008-04-09
基金项目:南京军区“十五”医药卫生科研基金(02MA009).
Protective effect of N-acetylcysteine on small intestine of male rats after irradiation
WANG Yu1△,ZHANG Zai-zhong1△,CHEN Shao-quan1,WANG Lie1* ,ZHENG Guo-hua2
(1.Research Institute of General Surgery,Fuzhou General Hospital,PLA Nanjing Military Area Command,Fuzhou 350025,China; 2.Department of Nursing,Fujian University of Traditional Chinese Medicine,Fuzhou 350000)
Abstract:
Objective:To evaluate the protective effect of N-acetylcysteine(NAC) on the small intestine of male rats after X ray irradiation of the whole abdominal region.Methods: Sixty male Spraque-Dawley rats were divided in normal control group (n=12),irradiation group(n=12),and NAC groups(50,200,and 300 mg/kg,n=12).Irradiation injury was induced with X ray at a single dose of 1 000 cGy(source-to-skin distance 80 cm) for the abdominal regions after the animals had been anesthetized with sodium thiopental(40 mg/kg,i.p.).NAC was started 3 days before irradiation and administered for 3 more days after irradiation,and then rats were euthanized after 12 h fasting.The terminal ileum samples were collected for crypt survival assay and counting in ileal villi.The blood samples were collected for examination of superoxide dismutase(SOD) activity,and the contents of malondialdehyde(MDA) and glutathione hormone(GSH) in the small intestine.The plasma levels of D-lactate and diamine oxidase(DAO) were also measured.Results: The mucosal structure of the terminal ileum was damaged after irradiation.The plasma levels of D-lactate,DAO and the content of MDA were significantly increased;the activity of SOD and the content of GSH were significantly decreased(P<0.01).NAC at different dosages increased crypt survival rates and the number of ileal villi in the terminal ileum(P<0.05,P<0.01),enhanced the activities of SOD and content of GSH(P<0.05,P<0.01),and deceased the concentrations of D-lactate,DAO and MDA(P<0.05,P<0.01).Conclusion: NAC may protect the small intestine from irradiation-induced injury by protecting the intestinal mucosal barrier,eliminating oxygen free radicals,and maintaining the internal oxidative balance and the structure and function of intestinal mucous.
Key words:  N-acetylcysteine  small intestine  radiation injuries  radiation protection  radiation enteritis  intestine barrier functional disturbance