| Objective:Hypoxia is a basic pathological process in a lot of clinical diseases and the most common injury factor in cardiovascular and cerebrovascular diseases, thoracic qi was composed of the fresh air in the nature and the essence of water and grain transported and transformed by the spleen and stomach. The shortage of the fresh air in the nature for a long-term may cause the occurrence of thoracic qi-deficiency.This study were from the relevance of hypoxia and Chinese medicine thoracic qi-deficiency, to discuss the effects of Tongxinluo(TXL) on the ability of anti-hypoxia and vascular endothelial function in acute and chronic hypoxia animals and preliminarily to investigate its mechanism of action, to provide experimental basis on the effective prevention and cure of hypoxia and circulatory disease which taking hypoxia as pathology foundation.Methods:1 The effect of TXL on the ability of anti-hypoxia in the acute and chronic hypoxia animals1.1 Experiment 1 the effect of TXL on the survival time in the acute hypoxia miceForty healthy mice were randomly divided into 4 groups according to their weight and there are 10 rats in each group:the acute hypoxia model group, the TXL high dose group, the TXL medium dose group and the TXL low dose group. the rats of TXL groups were intragastric administration by TXL(1.52g,0.76g and 0.38g crude drug per kg respectively)according to 1ml/10g, the mice were given medicine for three days, the acute model group was intragastric administration by saline. After intragastric administration for one hour at the last day, the survival time was measured.1.2 Experiment 2 the effect of TXL on arterial blood gas analysis in the chronic hypoxia rats.Forty healthy male Wistar rats of sanitary degree were randomly divided into 4 groups according to their weight and there are 10 rats in each group:the blank control group, the hypoxia model group, the TXL high dose group and the TXL low dose group. The hypoxia model group was put into normal pressure hypoxia cabin, 7 hours in every day and 6 days in every weeks, at the basis of the hypoxia model group,the rats of TXL groups were intragastric administration by TXL(1.2g crude drug /kg/d and 0.6g crude drug per kg respectively)which was suspended by CMC-Na according to 1ml/100g, the experiment was add up to 5 weeks, in the end of the experiment ,the arterial blood carbon dioxide partial pressure(PaCO2), blood pressure (PaO2)and oxygen saturation(SaO2).were detected by arterial blood gas analysis instrument. 2 The effect of hypoxia on the function of blood vessel endothelium and the intervention effect of TXLExperimental animal, the method of dividing group and establishing model were the same as experiment 2. At the endpoint of experiment, the morphological changes of aorta thoracica observed by light microscope and the ultramicrostructure changes of aorta observed by transmission electron microscope. The concentration of plasma endothelian (ET)was detected with radioimmunoassay, serum nitro oxygen (NO) was detected with nitrate reductase, and plasma von wilebrand factor (vWF) was detected with ELISA.3 The effect of hypoxia on NEI network and the the intervention effect of TXLExperimental animal, the method of dividing group and establishing model were the same as experiment 2. At the endpoint of experiment, the NEI network indexes were detected as following:Hypothalamo-pituitary-adrenal axis(HPAA): corticotrophin releasing hormone(CRH) of hypothalamus, adrenocorticotrop(h)ic hormone(ACTH) in plasma, corticosterone(CORT)in serum were detected by Radio-immunity Approach. Nor-epinephrine and epinephrine in serum was detected by ELISA Approach. The correlation between endothelial function index and the NEI network correlative factors was analyzed with canonical correlative analysis method. At the same time, the effects of TXL were studied.Results:1 The effect of TXL on the ability of anti-hypoxia in the acute and chronic hypoxia animals1.1 Observation of general conditionAt the beginning of the experiment, the mice were very active, with time going, the mice were dysphoretic, breathing was accelerated. With more and more severe hypoxia, the skin of mice were white, the color of lip were cyanosed, then the mice frightening and jumping, fidgeting, limbs convulsing, the head to the back, breathing holding and dead in the end.1.2 the effect of TXL on the survival time in the acute hypoxia miceCompared with the survival time (34.61±4.64)in the blank control group, the survival time (47.83±4.74)of TXL high dose group, the survival time (43.67±9.36)of TXL medium dose group and the survival time (44.14±7.66)of TXL low dose group were all obviously increased((P<0.01)), but no significant difference was observed in the TXL groups(P>0.05).1.3 the effect of TXL on blood gas analysis in the chronic hypoxia rats.Compared with the blank control group, PaO2 in the hypoxia model group was obviously decreased, PaCO2 and SaO2 had no significant difference (P>0.05).Compared with the hypoxia group, PaO2 in the TXL groups were significantly increased (P<0.05), and PaCO2 and SaO2 had no significant difference (P>0.05).2 The effect of hypoxia on the function of blood vessel endothelium and the intervention effect of TXL2.1 He staining showed thatThe blank control group: The morphous of intima, tunica media and adventitial coat were almost normal and structure was integrated.The hypoxia group: endothelial cells were engorge, maldistribution. The density increased. Intima thickened. There were many lymph-cell and inflammatory cells in the tunica intima. Smooth muscle cells were edema. Elastic fibers were thin.The TXL high dose group: endothelial cells were engorge, Internal elastic plate were almost integrated; Smooth muscle cells were lightly edema. Elastic fibers were thin.The TXL low dose group: endothelial cell were almost normal, The density increased or disappeared. Internal elastic plate were almost integrated Smooth muscle were edema, Elastic fibers were thin.2.2 Transmission electron microscope showed thatThe blank control group: Endothelial cell morphology was integrity and connection was tight. The basal lamina was integrity. Cell nucleus and cell organelle were exist. The structure of chondriosome had no abnormalities.The hypoxia group: some crests of mitochondria of vascular endothelial cells fused with membrance, and even disappeared. The degranulation of rough endoplasmic reticulum was obvious. The number of pinocytosis vesic was decreased.The TXL high dose group: crests of mitochondria of vascular endothelial cells fused with membrance, and disappeared. The degranulation of rough endoplasmic reticulum was obvious.The TXL low dose group: crests of mitochondria of vascular endothelial cells fused with membrance, and disappeared, The degranulation of rough endoplasmic reticulum was obvious. The number of pinocytosis vesic was decreased.2.3 The changes of biochemical indicator related to Vascular endothelialCompared with the blank control group, the plasma ET and vWF of rats in the hypoxia model group were significantly increased (P<0.01), and the content of NO were significantly decreased (P<0.01).Compared with the hypoxia group, the plasma ET and vWF were significantly decreased (P<0.01), and the level of NO were significantly increased in TXL high and low dose groups (P<0.05 or P<0.01)3 The effect of hypoxia on NEI network and the the intervention effect of TXL3.1 the change of HPAACompared with the blank control group, the content of CRH of rats in the hypoxia model group were significantly decreased; the content of ACTH and CORT were significantly increased (P<0.01).Compared with the hypoxia group, the content of CRH of rats in the TXL groups were significantly increased (P<0.01), the level of ACTH and CORT were significantly decreased (P<0.05 or P<0.01)3.2 the change of sympathesis-adrenal medulla systemCompared with the blank control group, the level of E and NE of rats in the hypoxia model group were significantly increased (P<0.05 or P<0.01)Compared with the hypoxia group, the level of E in the TXL high dose group was significantly decreased in the TXL high dose group, but there have no significantly change in TXL low dose group; the level of NE were significantly decreased in the TXL groups (P<0.01)Conclusions:1 TXL can significantly extend the survival time under conditions of acute hypoxia in mice, improve oxygen partial pressure under the conditions of chronic hypoxia in rats, showing TXL can enhance hypoxia tolerance of animals2 Hypoxia can cause obvious vascular endothelial injury and dysfunction, TXL can significantly improve the impaired endothelial function.3 Under hypoxic conditions, there exist the disturbance of NEI network and the main manifestation were hypersplenism of the sympathetic - adrenal system and the hypothalamus - pituitary - adrenocortical axis. Canonical correlation analysis showed that there was correlation between vascular endothelial function-related factor and NEI network -related factor in hypoxia rats, showing that the disturbance of NEI network was probably one of the mechanisms of vascular endothelial injury under the hypoxic condition.4 TXL improving vascular endothelial function mechanism under the conditions of hypoxia was related to regulating the imbalances on the sympathetic - adrenal system and the hypothalamus - pituitary - adrenocortical axis.
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