莫沙必利对模拟急性高原暴露大鼠小肠动力的改善作用

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目的观察莫沙必利对高原缺氧大鼠小肠动力及黏膜屏障的保护作用,初步探讨其对肠道急性缺氧损害的预防作用。方法将90只SD雄性大鼠按随机数字表法分为正常对照组、高原缺氧组、高原莫沙必利组;低压氧舱模拟海拔6 000 m,氧分压(9.31±0.05)kPa,氧含量(19.6±0.2)%,建立大鼠急性缺氧模型,高原莫沙必利组采用莫沙必利灌胃,3次/d,每天剂量0.27 mg/kg。分别于10、24、48、72、168 h取小肠组织。检测急性高原缺氧应激后小肠组织一氧化氮(NO)、一氧化氮合酶(NOS)的含量变化;墨汁灌胃实验计算推进距离,检测小肠动力;RT-PCR检测小肠黏膜闭锁连接蛋白1(ZO-1)mRNA的表达情况。结果与同时间段正常对照组比,高原缺氧组NO、NOS含量增高,24、48、72、168 h NO含量差异明显(P<0.05,P<0.01),48、72、168 h NOS含量差异明显(P<0.05,P<0.01);ZO-1 mRNA表达量降低,48、72、168 h差异明显(P<0.05,P<0.01);高原莫沙必利组NO、NOS含量较正常对照组增高,仅48 h NO含量增高明显(P<0.05);高原缺氧组与高原莫沙必利组(168 h除外)各时间点小肠推进距离均较正常对照组明显降低(P<0.05,P<0.01)。各时间点高原莫沙必利组NO、NOS含量较高原缺氧组降低,72 h NO,72、168 h NOS含量差异明显(P<0.05);各时间点高原莫沙必利组小肠推进距离及ZO-1 mRNA的表达量较高原缺氧组增高,48、72、168 h的小肠推进距离及72、168 hZO-1 mRNA的表达量差异明显(P<0.05)。结论莫沙必利可有效促进小肠动力,减轻高原缺氧应激引起的小肠动力障碍及肠道黏膜屏障的损伤,可用于高原缺氧肠道损害的预防。 Objective To observe the protective effects of mosapride on small intestine motility and mucosal barrier in rats with plateau hypoxia and to explore its preventive effect on acute intestinal hypoxia injury. Methods Ninety SD male rats were randomly divided into normal control group, hypoxia plateau group and high altitude mosapride group. The hypoxia chamber simulated altitude 6 000 m, partial pressure of oxygen (9.31 ± 0.05) kPa, Oxygen content (19.6 ± 0.2)%. The model of acute hypoxia in rats was established. Mosapride group in high altitude was treated with mosapride intragastrically for 3 times daily for 0.27 mg / kg. Small intestine tissue was taken at 10, 24, 48, 72 and 168 h respectively. The changes of nitric oxide (NO) and nitric oxide synthase (NOS) in small intestine after acute hypoxia stress were detected. The distance of propulsion was calculated by gavage in ink and the motility of small intestine was detected. The expression of small intestinal mucosal atresia 1 (ZO-1) mRNA expression. Results Compared with the normal control group at the same time, the content of NO and NOS in the anaerobic plateau increased and the content of NO in 24, 48, 72 and 168 h was significantly different (P <0.05, P <0.01) (P <0.05, P <0.01). The expression of ZO-1 mRNA was decreased in 48,72,168 h (P <0.05, P <0.01). Compared with normal (P <0.05). Compared with the control group, the intestinal propulsion distance at each time point in the plateau hypoxia group and the mosapride group (except 168 h) was significantly lower than that in the normal control group (P <0.05) , P <0.01). At each time point, the content of NO and NOS in the plateau was higher than that in the original hypoxia group, and the difference was significant (P <0.05) between 72 h and 72 h after 72 h. The intestinal propulsion distance The expression of ZO-1 mRNA was higher in hypoxia group than that in hypoxia group. The small intestine propulsion distance and the expression of 72,168 h ZO-1 mRNA at 48, 72 and 168 h were significantly different (P <0.05). Conclusion Mosapride can effectively promote the motility of small intestine, relieve the intestinal motility disorder and intestinal mucosal barrier injury caused by hypoxia stress in plateau, and can be used for the prevention of intestinal hypoxia injury in plateau.
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