N-乙酰半胱氨酸对大鼠辐射损伤相关肠屏障功能障碍的防护作用

目的探讨N-乙酰半胱氨酸（NAC）对大鼠小肠辐射损伤相关肠屏障功能障碍的防护作用及其作用机制。方法24只雄性SD大鼠随机分为3组，单纯照射组（8只）仅接受10Gyx线单次腹部照射：NAC治疗组（8只）予以10GyX线单次腹部照射并NAC（300mg／kg）腹腔注射7d（照射前4d开始给药，照射后3d停止给药）；正常对照组（8只）予以10％葡萄糖腹腔注射，注射时间同治疗组。照射后3d处死大鼠，取血桨、末端回肠、肝、脾及肠系膜淋巴结标本。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．测定血中D-乳酸、内毒素含量及二胺氧化酶（DAO）活性，检测小肠黏膜组织中一氧化氮（NO）水平，进行细菌培养以测定细菌易位率。结果辐射照射后，NAC治疗组大鼠肠腺存活率为（76．84±4．82）％，绒毛数量为（8．56±0．68）个／mm；与单纯照射组（49．64±5．48）％和（4．02±0．54）个／mm]比较。差异有统计学意义（均P〈0．01）。两组大鼠小肠黏膜组织中NO含量分别为（0．48±0．12）μmol／g和（0．88±O．16）μmol／g，差异有统计学意义（P〈0．01）。NAC治疗组大鼠血浆D-乳酸含量、DAO活性、内毒素水平及肠道细胞易位率与单纯照射组比较，差异均有统计学意义（P〈0．05或P〈0．01）。结论NAC对辐射损伤相关肠屏障功能障碍具有防护作用．可能与其抑制炎性介质NO的产生有关。

Protective effect of N-acetylcysteine on the intestinal barrier dysfunction after radiation injury in rats

Objective To evaluate the protective effect of N-acetylcysteine (NAC) on the intestinal barrier dysfunction in rats after extensive abdominal radiation with X ray. Methods Twenty-four Spraque-Dawley male rats were divided into normal control group (n=8), radiation group (n=8),and radiation+NAC group(300 mg/kg)(n=8). Radiation injury was induced by X ray with a single dose of 10 Gy. NAC was administered from 4 days before irradiation to 3 clays after radiation. Three days after radiation, all the rats were euthanized. The terminal ileum was collected for crypt survival assay and ileal villi count. The tissue samples from mesenteric lymph nodes (MLN), spleen, and liver were harvested under sterile conditions for microbiological analysis and ileum samples were harvested for biochemical analysis. The blood levels of D-lactate, endotoxin and diamine oxidase (DAO) and the ileum samples levels of nitric oxide (NO) were also measured. Results Rats in radiation + NAC group had a higher survival rate of intestinal crypt (76.84±4.82)% vs (49.64±5.48)%, P<0.01],higher intestinal villus count (8.56±0.68)/mm vs (4.02±0.54)/mm, P<0.01], lower NO concentration (0.48±0.12) μmol/g vs (0.88±0.16) μmol/g, P<0.01], lower levels of D-lactate, endotoxin and DAO (P<0.05 or P<0.01), and significantly decreased enteric bacteria cultured from mesenteric lymph nodes and other tissues as compared with the radiation group(P<0.05 or P<0.01). Conclusion NAC protects the small intestine from radiation-induced injury maybe through the inhibition of NO in rats.