【摘要】 目的 探讨白藜芦醇对直肠癌放疗大鼠肠道损伤的影响及其作用机制。方法 研究对象选取健康大鼠18只，均建立直肠癌模型。建立后随机均分为对照组及白藜芦醇组，每组9只，对照组给予安慰剂，白藜芦醇组给予20 mg·kg^-1·d^-1白藜芦醇，两组均给予单剂量5Gy放疗。连续干预3周后比较两组大鼠氧化应激（ROS）标志物、炎性因子介质表达水平；观察两组大鼠肠道病理组织学变化，使用TUNEL染色观察两组肠道绒毛、隐窝细胞凋亡；使用蛋白印迹检测两组大鼠PI3K、AKT、m TOR蛋白表达。结果 白藜芦醇组MDA水平显著低于对照组，HSH、CAT水平显著高于对照组，差异有统计学意义（P<0.05）；白藜芦醇组TNF-α、NF-κB、IL-1β水平显著低于对照组，差异有统计学意义（P<0.05）；白藜芦醇组绒毛、隐窝细胞凋亡率低于对照组，差异有统计学意义（P<0.05）；白藜芦醇组PI3K、Akt和mTOR蛋白相对表达量显著低于对照组，差异有统计学意义（P<0.05）；病理组织学检测显示，对照组肠黏膜部分绒毛尖端坏死，固有层白细胞炎症细胞浸润，绒毛高度和宽度杂乱，部分绒毛可见缩短、萎缩，增生和多动杯状细胞出现，出现肠道损伤，白藜芦醇组肠道损伤缓解，肠道组织结构改善。结论 白藜芦醇通过抑制PI3K/Akt/mTOR通路，在改善放疗诱导的ROS产生和炎症方面具有潜在的治疗价值，可减轻放疗大鼠肠道炎症并减少大鼠肠道绒毛、隐窝细胞凋亡。白藜芦醇可能可作为一种有前景的放疗辅助剂，通过减少放疗后的肠道并发症来提高治疗效果和安全性。更多还原

【Abstract】 Objective To explore the effect of resveratrol on intestinal injury in rats with rectal cancer radiotherapy and its mechanism. Methods All 18 healthy rats were selected to establish rectal cancer model. After establishment,all patients were divided into control group and resveratrol group,with 9 patients in each group. The control group was given placebo,the resveratrol group was given resveratrol 20 mg·kg^-1·d^-1,and both groups were given a single dose of 5 Gy radiotherapy. After 3 weeks of continuous intervention,the expression levels of oxidative stress（ROS）markers and inflammatory factor mediators were compared between the two groups. The intestinal histopathological changes of rats in two groups were observed,and the apoptosis of intestinal villus and crypt cells in two groups was observed by TUNEL staining. The expressions of PI3K,AKT and mTOR were detected by Western blot. Results The MDA level of the resveratrol group was significantly lower than that of the control group,and the HSH and CAT levels were significantly higher than those of the control group,with statistical significance（P<0.05）. The levels of TNF-α,NF-κB and IL-1β in the resveratrol group were significantly lower than those in the control group,and the difference was statistically significant（P<0.05）. The apoptosis rate of villus and crypt cells in the resveratrol group was lower than that in the control group,and the difference was statistically significant（P<0.05）. The relative protein expressions of PI3K,Akt and mTOR in the resveratrol group were significantly lower than those in the control group,with statistical significance（P<0.05）. Histopathological examination showed that part of the intestinal mucosa in the control group was necrotic at villus tip,infiltration of leukocyte inflammatory cells in lamina propria,disorganized villi in height and width,shortening and atrophy,hyperplasia and hyperactive goblets appeared in part of the villi,and intestinal damage was observed. In the resveratrol group,intestinal damage was relieved and intestinal tissue structure was improved. Conclusion Resveratrol has potential therapeutic value in improving ROS production and inflammation induced by radiotherapy by inhibiting PI3K/Akt/mTOR pathway,alleviating intestinal inflammation and reducing intestinal villus and crypt cell apoptosis in rats treated with radiotherapy. Resveratrol may be a promising adjuvant to radiotherapy to improve therapeutic efficacy and safety by reducing intestinal complications after radiotherap.更多还原