摘要
目的观察姜黄素灌胃对脂肪肝大鼠肠黏膜屏障损伤的改善作用,并探讨其作用机制。方法应用高脂饲料喂养SD大鼠建立脂肪肝模型后,分为模型组、姜黄素低剂量组、姜黄素高剂量组,每组10只;普通饲料喂养的SD大鼠10只,记为对照组。各组大鼠喂养8周后,姜黄素低剂量组给予200 mg/(kg·d)姜黄素灌胃,姜黄素高剂量组给予400 mg/(kg·d)姜黄素灌胃,对照组和模型组大鼠予以羧甲基纤维素钠灌胃,各组大鼠灌胃8周后处死。取各组大鼠肝脏、小肠组织,HE染色后光镜下观察病理学变化。取大鼠门静脉血,测定门静脉血浆LPS、二胺氧化酶(DAO)及血清ALT、AST。取小肠组织,测定丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性,采用Western Blotting法检测小肠组织中核因子-E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)蛋白。结果对照组大鼠肝细胞结构正常,模型组肝细胞内可见大小不等的脂肪堆积,姜黄素低剂量组、姜黄素高剂量组肝细胞脂肪变减轻;对照组绒毛无充血及水肿,模型组绒毛结构破坏,姜黄素低剂量组、姜黄素高剂量组绒毛缺失减少。与对照组相比,模型组、姜黄素低剂量组、姜黄素高剂量组大鼠血浆LPS、DAO及血清AST、ALT水平均升高(P均<0.05),但姜黄素低剂量组、姜黄素高剂量组低于模型组(P均<0.05),且有剂量依赖性(P均<0.05)。与对照组相比,模型组、姜黄素低剂量组、姜黄素高剂量组大鼠小肠组织MDA含量均升高(P均<0.05),但姜黄素低剂量组、姜黄素高剂量组低于模型组(P均<0.05),且有剂量依赖性(P均<0.05);与对照组相比,模型组、姜黄素低剂量组、姜黄素高剂量组大鼠小肠组织SOD活性均降低(P均<0.05),但姜黄素低剂量组、姜黄素高剂量组高于模型组(P均<0.05),且有剂量依赖性(P均<0.05)。与对照组相比,模型组、姜黄素低剂量组、姜黄素高剂量组大鼠小肠组织中Nrf2、HO-1蛋白相对表达量均升高(P均<0.05),且姜黄素低剂量组、姜黄素高剂量组高于模型组(P均<0.05),且有剂量依赖性(P均<0.05)。结论姜黄素灌胃可改善脂肪肝大鼠的肠黏膜屏障损伤,其作用机制可能与激活Nrf2/HO-1通路改善肠道氧化应激状态有关。
Objective To observe the improvement effect of the intragastric administration of curcumin on intestinal mucosal barrier injury rats with fatty liver,and to explore its mechanism of action.Methods Non-alcoholic fatty liver disease rat models were established by high-fat diet,and then were randomly divided into the high fat group,low-dose cur-cumin group,and high-dose curcumin group,with 10 mice in each group.Anther 10 normal rats were used as the control group.Rats in low-dose curcumin group were given curcumin 200 mg/(kg·d)by gavage,while rats in the high-dose group were given curcumin 400 mg/(kg·d)by gavage.Rats in the control and model groups were given sodium carboxy-methyl cellulose by gavage,and rats in each group were sacrificed after 8 weeks of gavage.We took the liver and small in-testine tissues from rats of each group,and observed pathological changes under light microscopy by HE staining.We took the portal vein blood from rats and measured LPS,diamine oxidase(DAO),ALT and AST.The small intestine tissues were taken to measure the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD).Western blotting was used to detect nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in the small in-testine tissues.Results Hepatocyte architecture was normal in the control group.Lipid droplets of varying sizes were seen in hepatocytes of the model group.Hepatocellular steatosis was attenuated in the low-dose group and high-dose group.The villi of rats in the control group showed no congestion and edema,while the villi of rats in the model group showed structural damage.The villi of rats in the low-dose and high-dose curcumin groups showed loss and reduction.Compared with the control group,the blood levels of DAO,LPS,AST,and ALT in the model group,low-dose curcumin group,and high-dose curcumin group increased(all P<0.05).However,those in the low-dose and high-dose curcumin groups were lower than those of the model group(all P<0.05),with a dose-dependent manner(all P<0.05).Compared with the control group,MDA content of intestine in the model group,low-dose curcumin group,and high-dose curcumin group increased(P<0.05),but that in the low-dose and high-dose curcumin groups was lower than that of the model group,with a dose-dependent manner(P<0.05).Compared with the control group,SOD activity of intestine in the model group,low-dose curcumin group,and high-dose curcumin group decreased(P<0.05),but that in low-dose curcumin group and high-dose curcumin group was higher than model group,with a dose-dependent manner(P<0.05).Compared with the control group,the SOD activity of small intestine tissues in the model group,low-dose curcumin group,and high-dose curcumin group decreased(all P<0.05),but that in the low-dose curcumin group and high-dose curcumin group was higher than that in the model group(all P<0.05),with a dose-dependent manner(all P<0.05).Compared with the con-trol group,the relative expression levels of Nrf2 and HO-1 proteins in the small intestine tissues of the model group,low-dose curcumin group,and high-dose curcumin group increased(all P<0.05),and those were higher in the low-dose cur-cumin group and high-dose curcumin group than in the model group(all P<0.05),and there was in a dose-dependent man-ner(all P<0.05).Conclusion Intragastric administration of curcumin can alleviate intestinal mucosal barrier damage in rats with fatty liver,and its mechanism of action may be related to activating the Nrf2/HO-1 pathway to improve intesti-nal oxidative stress status.
作者
侯洪涛
张建
裘艳梅
李苹苹
郑吉敏
王玉珍
刘改芳
HOU Hongtao;ZHANG Jian;QIU Yanmei;LI Pingping;ZHENG Jimin;WANG Yuzhen;LIU Gaifang(Department of Gastroenterology,People's Hospital of Hebei Province,Shijiazhuang 050051,China;不详)
出处
《山东医药》
CAS
2024年第9期47-51,共5页
Shandong Medical Journal
基金
河北省医学科学研究重点课题计划(20210710)。
