消痰化瘀利窍方对慢性间歇性低氧大鼠肠系膜动脉损伤的改善作用

目的:观察消痰化瘀利窍方对慢性间歇性低氧(CIH)大鼠肠系膜动脉功能损伤的作用,并探讨其可能机制。方法:48只雄性SD大鼠随机分为4组(n=12),常氧对照组(Normoxia)、慢性间歇性低氧组(CIH)、慢性间歇性低氧中药干预组(Formula+CIH)、中药对照组(Formula)。CIH与Formula+CIH组置于间歇性低氧装置,通过充入氮气、氧气使O2含量在9%至21%间循环,每循环3min;Normoxia和Formula组则充入空气。其中,Formula+CIH与Formula组于每日造模前中药水煎液灌胃(24g/kg),而CIH组与Normoxia组给予等量生理盐水。造模结束后,应用HE染色观察各组大鼠肠系膜动脉的组织病理学改变,通过微血管环技术观察ACh、L-Arg诱导的肠系膜动脉舒张反应,通过ELISA技术检测大鼠造模前及造模21d血清一氧化氮(NO)的含量并应用Westernblot技术测定肠系膜动脉eNOS和p-eNOS的蛋白水平。结果:与Normoxia组相比,CIH组大鼠肠系膜动脉内皮明显损伤、中膜增厚,ACh、L-Arg诱导的肠系膜动脉舒张反应明显减弱,血清中NO水平及肠系膜动脉p-eNOS/eNOS比值显著降低。消痰化瘀利窍方干预能够减轻大鼠肠系膜动脉的内膜与中膜病理损伤,改善肠系膜动脉舒张功能,提高血清NO含量及肠系膜动脉eNOS磷酸化水平。而单纯给予消痰化瘀利窍方大鼠与Normoxia组相比各指标均未发现显著变化。结论:消痰化瘀利窍方可以减轻慢性间歇性低氧引起的大鼠肠系膜动脉功能损伤,其机制与提高NO的生物利用度有关。

The effects of Xiaotan Huayu Liqiao formula on mesenteric artery function in rats exposed to chronic intermittent hypoxia

Objective: To investigate the effects of Xiaotan Huayu Liqiao formula (the Chinese Medicine) on mesenteric artery function in rats exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanism. Methods: Forty-eight male SD rats were randomly divided into four groups as Normoxia, CIH, Formula+CIH and formula group. Rats were exposed to normoxia in the Normoxia and Formula group, or intermittent hypoxia in CIH or Formula+CIH group. Xiaotan Huayu Liqiao formula was given at 24g/kg by intragastric administration before intermittent hypoxia exposure. The pathological changes of mesenteric artery were determined by HE staining, and the relaxation of mesenteric artery (induced by acetylcholine(ACh) and L-arginine(L-Arg)) was recorded by microvascular ring technique. Serums of all rats were collected (0 d and 21 d) and the content of NO was detected by ELISA. The levels of endothelial nitric oxide synthase (eNOS) and p-eNOS were measured by Western blot. Results: Compared with Normoxia group, the mesenteric arterial endothelial injury and media thickening were observed and the relaxation of mesenteric artery was significantly reduced in rats exposed to CIH. The level of NO in serum and the ratio of p-eNOS/eNOS were also decreased in the CIH group. Xiaotan Huayu Liqiao formula administration improved the pathologic changes and dilatation function of mesenteric artery, increased the levels of NO and p-eNOS. Compared with Normoxia group,all the results were not observed significant difference in Formula group. Conclusion: Xiaotan Huayu Liqiao formula increased the bioavailability of NO, and ameliorated the CIH induced mesenteric artery function injury.