Effect Of Xiaotan Huayu Liqiao Formula On Cardiovascular Injury And The Mechanisms In Chronic Intermittent Hypoxia Rats

Obstructive sleep apnea(OSA)is characterized by apnea or hypopnea,episodes of upper respiratory tract obstruction,decreased blood oxygen saturation,and sleep fragmentation during sleep.Chronic intermittent hypoxia(CIH)is the main pathologic feature in OSA patients.In recent years,the morbidity of OSA increased significantly and patients with OSA occur in 2%-4% adult males and 1%-2% adult females.Evidences indicated that OSA related risks for cardiovascular diseases,such as systemic hypertension,atherosclerosis,myocardial ischemia and stroke.Modern medicine for OSA patients generally were treated by continuous positive airway pressure treatment(CPAP),oral appliance treatment,surgical treatment.However,so far,these treatment measures have some disadvantages.Many researches indicated that CIH induced injury of cardiac function by oxidative stress,sympathetic system activation and endothelial dysfunction.In addition,the structural and functional impairment of resistance vessel,including mesenteric artery,were induced by CIH.Xiaotan Huayu Liqiao Formula can markedly improve the clinical symptoms of patients,such as somnolence,amnesia and dizziness,and effectively alleviate the occurrence and development of hypertension and other complications.In this study,the effects of Xiaotan Huayu Liqiao Formula on the cardiovascular injury in CIH rats were researched as follows.1.Effect of Xiaotan Huayu Liqiao Formula on the injury of cardiac function in CIH ratsObjective: The purpose of this study is to investigate the effect of Xiaotan Huayu Liqiao Formula on hypertension and myocardial injury in rats exposed to 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 in CIH or Formula+CIH group were placed in transparent plastic chambers.Thus,the concentration of oxygen in the chamber changed from 21% to 9% every 3 min.The exposure cycle was repeated for 8 h/day,7 days/weeks for 3 weeks.Normoxia and Formula group rats were always treated with room air.Xiaotan Huayu Liqiao Formula was given at 24g/Kg by intragastric administration before intermittent hypoxia exposure.Systolic blood pressure(SBP)was measured by BP-2000 and the renal sympathetic nerve activity(RSNA)was recorded by PowerLab signal acquisition system.Serums of all rats were collected and the content of NE was measured by ELISA.The left ventricles in all groups were weighed,and the pathological examination were observed(HE staining and Masson staining).Results: The blood pressure was gradually increased followed CIH exposure on the 7th,14 th and 21 st days.The RSNA and level of ET-1 in serum were increased in rats exposed to CIH compared with the Normoxia group.Furthermore,left ventricular hypertrophy and myocardial fibrosis were observed in rats exposed to CIH.Xiaotan Huayu Liqiao Formula administration significantly decreased SBP,reversed the increased RSNA and ameliorated the myocardial injury.Conclusion: Xiaotan Huayu Liqiao Formula inhibited RSNA and hypertension in rats exposed to CIH,and improved the CIH induced myocardial injury.2.Effect of Xiaotan Huayu Liqiao Formula on the mesenteric artery injury in CIH ratsObjective: The purpose of this study is to investigate the improvement of Xiaotan Huayu Liqiao Formula on mesenteric artery function in rats exposed to CIH,and to explore the related mechanism.Methods: The methods of CIH exposure and treatment were same as part1.HE staining examinated that the pathological change of mesenteric artery,and the relaxation of mesenteric artery(induced by Ach and L-Arg)were recorded by microvascular ring technique.Serums of all rats were collected(0d and 21d)and the content of NO was detected by ELISA.The level of e NOS and p-e NOS were measured by Western blot.Results: Compared with Norm group,the mesenteric arterial endothelial injury and media thickening were observed and the relaxation of mesenteric artery were significantly reduced in rats exposed to CIH.The level of NO in serum and the ratio of p-e NOS/e NOS were also decreased in the CIH group.Xiaotan Huayu Liqiao Formula administration improved the pathologic changes and dilatation function of mesenteric artery,increased the level of NO and p-e NOS.Conclusion: Xiaotan Huayu Liqiao Formula increased the bioavailability of NO,and ameliorated the CIH induced mesenteric artery function injury.