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目的:研究熊果酸(Ursolic acid,UA)对大鼠肠系膜缺血再灌注损伤的保护作用,并探讨其作用机制。方法:将120只清洁级雄性Wistar大鼠随机分假手术组、肠系膜缺血再灌注模型对照组、熊果酸(40、80和120mg/kg)预防组,银杏叶提取物(3.15mg/kg)阳性对照组,每组20只;采用夹闭肠系膜上动脉45 min后去夹的方法制备肠系膜缺血再灌注损伤大鼠模型,于再灌注前10min迅速通过尾静脉给药。再灌注6h后,观察各组大鼠肠组织外观并测定含水量(IWC);通过苏木精-尹红(HE)染色观察肠组织病理学改变并进行肠组织损伤评分(Chiu’s氏评分);通过原位末端转移酶标记染色(TUNEL染色)的方法观察肠组织细胞凋亡状况并进行凋亡指数评分;检测肠系膜组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和内毒素水平;检测肠组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量。结果:与肠系膜缺血再灌注模型对照组相比,熊果酸治疗组大鼠肠组织颜色明显变红润,熊果酸80、120 mg/kg预防组含水量显著降低;肠组织病理学改变明显减轻,其中熊果酸80、120 mg/kg预防组Chiu’s氏评分显著降低;肠组织凋亡状况明显减轻,其中熊果酸80、120 mg/kg预防组凋亡指数评分显著降低;熊果酸80和120 mg/kg预防组大鼠肠组织中TNF-α、IL-1β、IL-6和内毒素表达水平显著下降且IL-10水平和SOD,CAT活性显著升高,熊果酸80和120 mg/kg预防组大鼠肠组织中MDA含量显著降低;上述作用以熊果酸120 mg/kg预防组最为显著。结论:熊果酸对大鼠肠系膜缺血再灌注损伤具有剂量依赖性的保护作用,其作用机制可能与熊果酸能够有效改善抗氧化酶活性、抑制氧化应激损伤,抑制炎症反应,改善肠组织病变并抑制肠细胞凋亡有关。
Objective: To study the protective effect of Ursolic acid (UA) on rat mesenteric ischemia-reperfusion injury and to explore its mechanism. Methods: Totally 120 male Wistar rats of clean grade were randomly divided into sham operation group, model group of mesenteric ischemia / reperfusion injury, prevention group of ursolic acid (40, 80 and 120 mg / kg), Ginkgo biloba extract (3.15 mg / kg ) Positive control group, 20 rats in each group. Mesenteric ischemia-reperfusion injury rat model was prepared by clipping the superior mesenteric artery for 45 min and then rapidly through tail vein administration 10 min before reperfusion. After 6h of reperfusion, the appearance of intestinal tissue of rats in each group was observed and the water content (IWC) was measured. The pathological changes of intestinal tissue were observed by hematoxylin-eosin (HE) staining and the intestinal tissue damage score (Chiu’s score) The apoptosis of intestinal mucosa was observed by TUNEL staining and the apoptotic index was measured. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL) 1β, IL-6, IL-10, and endotoxin were measured. The activities of superoxide dismutase (SOD), catalase (CAT) And malondialdehyde (MDA) content. Results: Compared with the model group, the color of uric acid in the ursolic acid treatment group was significantly ruddy, and the water content of the ursolic acid 80 and 120 mg / kg prophylaxis group was significantly reduced. The pathological changes of intestinal tissue were obvious Reduce the Chiu’s’ s score of 80 and 120 mg / kg group, and significantly reduce the apoptosis of intestinal tissue, in which, the apoptosis index score of 80 and 120 mg / kg group of ursolic acid was significantly decreased; The levels of TNF-α, IL-1β, IL-6 and endotoxin in the intestinal mucosa of 80 and 120 mg / kg prophylaxis groups were significantly decreased and the levels of IL-10 and SOD and CAT were significantly increased In the 120 mg / kg prophylaxis group, the content of MDA in the intestinal tissue of rats in the prevention group was significantly decreased. The above effects were the most significant in the prevention group of ursolic acid 120 mg / kg. CONCLUSION: Ursolic acid can protect rat mesenteric ischemia-reperfusion injury in a dose-dependent manner. The mechanism may be related to that ursolic acid can effectively improve antioxidant enzyme activity, inhibit oxidative stress injury, inhibit inflammatory reaction and improve intestinal Tissue lesions and inhibition of intestinal apoptosis.