莫沙必利对模拟急性高原暴露大鼠小肠动力的改善作用

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。

Mosapride promotes small intestine motility in acute high altitude-exposed rats

Objective To determine the preventive effect of mosapride in the power of small intestine and mucosal barrier in rats in high altitude environment,and investigate its preventive role in intestinal injury induced by acute hypoxia.Methods A total of 90 SD male rats were randomly divided into 3 groups,that is,normal control group,hypoxia model group and hypoxia+mosapride treatment group(n=30).The rats from the 2 later groups were exposed to 6 000-meter high altitude in a hypobaric chamber under oxygen partial pressure(9.31±0.05) kPa and containing oxygen(19.6±0.2)% to establish rat model of acute hypoxia.At the same time,the animals of hypoxia+mosapride treatment group were gavaged with mosapride 0.27 mg/(kg·d),3 times per day].The rats were killed in 10,24,48,72,and 168 h respectively,and their small intestine tissues were taken for content of nitric oxide(NO) and activity of nitric oxide synthase(NOS).The motility of small intestine was evaluated by calculating the promotion distance of the ink which was fed in 30 min before sacrifice.RT-PCR was employed to detect the expression of ZO-1 in small intestine.Results Compared with the normal control group,NO content and NOS activity in the model group were significantly increased,and the expression of ZO-1 mRNA was significantly decreased,especially the expression in 48 h(P<0.05).So did the promote distance of small intestine were significantly lower at all time points(P<0.05).Though the hypoxia+mosapride group had above mentioned changes,mosapride obviously attenuated them when compared with model group.NO content at 72 h,NOS activity and ZO-1 mRNA expression at 72 and 168 h,and promotion distance of small intestine at 48,72 and 168 h in mosapride treatment group were significantly improved(P<0.05).Conclusion Mosapride promotes the power of small intestine effectively,reduces the disorders of small intestine power and the damage of intestinal mucosal barrier induced by high altitude stress,and it can be used to prevent intestinal damage in altitude.