| To investigate the mechanism of action of endothelial cell adhesion molecule-1expression in Dao Tan Tang intervention with carotid atherosclerosis from the "artery turbid"This study on the basis of the theory of traditional Chinese medicine, the concept of the Chinese medicine "arterys turbid", as the starting point of modern medical research, on the the Dao Tan soup intervention mechanism for the interpretation of carotid atherosclerosis.Artery is one of extraordinary fu-visceras, with relative independence and integrity."Arterys turbid" is caused by both "weakened body resistance" and "evil damage", and two factors affect each other and the transformation of their disease is "artery" bit, the vacuity arterys cloud pathogenesis key. The carotid atherosclerosis embodied in the form as artery turbid of a specific incidence with the accelerated process of population aging and rising.TCM theory holds that phlegm resistance is an important pathological basis of carotid atherosclerosis and pathogenic factors. Dao Tan Decoction (DTD), as a prescription to the commonly used clinical phlegm, could treat phlegm dampness. DTD, which could used in the phlegm treatment, also has a specific role in the process of carotid atherosclerosis, yet lacking of a large number of in-depth fundamental research.The activation of endothelial cell injury and endothelial cell adhesion molecule-1(intercel lular adhesion molecular-1, ICAM-1) are the star t ing part s of atherosclerosis. Expression of ICAM-1and mitogen-activated protein kinase family, JNK and p38pathway and ICAM-1expression between closely related. In addition, p53, p21and other tumor suppressor genes are key effectors of cellular senescence; p53/p21pathway can be directly induced ICAM-1over-expression of the endothel ial cells in carotid atheroscleros is and other age-related dis eases.Therefore, this study was under the guidance of the theory of the artery turbidity. DTD intervention would be used in vitro, in vivo models based on analysis ICAM-1expression in the carotid atherosclerosis. It was found:I. DTD interfere with the expression of ICAM-1via JNK, p38signaling pathway In animal experiments, the control group carotid intimal integrity, in the film spindle smooth muscle cells, blood vessel wall with a small amount of ICAM-1, JNK and p38positive cells. Plaque formation in model group intimal obvious thickening, subintimal accumulation of a large number of foam cells in the cytoplasm of the vascular wall foam cells, smooth muscle cells and endothelial cells, ICAM-1, JNK and p38strongly positive expression significantly higher (p<0.01). DTD, and mild in the low-dose group, endometrial hyperplasia, subintimal only a small amount of foam cell formation, to a lesser degree in the model group, DTD group of cells within the expression of ICAM-1, JNK, and p38positive expression significantly lower than the model group, see, in the high-dose group of ICAM-1and JNK inhibition was significantly stronger than the low-dose group (p<0.01), the high-dose group p38inhibition was stronger in the small dose group (p<0.01). The correlation analysis showed that, JNK, and ICAM-1levels were significantly positively correlated (p<0.01). p38and ICAM-1levels were significantly positively correlated (p<0.01).In vitro experiments, It was found that TNF-α-induced expression of ICAM-1, JNK activity and p38activity were significantly higher than the normal control group and DTD the control group (p<0.01). DTD containing serum or SB203580treatment, ICAM-1express ion was significant ly decreased (p<0.05). In10%,20%DTD containing serum or SP600125treatment, JNK activity was significantly decreased (p<0.01).20%DTD containing serum or SB203580treatment, p-p38expression was significantly decreased (p<0.05). The correlation analysis showed that JNK activity and p38act ivi ty and ICAM-1mRNA level was significantly positively related (p<001).II. DTD interfere with the expression of ICAM-1via p53, p21pathwayThere is a small amount of ICAM-1, p53and p21positive cells, in vessel wall of the normal control group. Strong positive expression of ICAM-1, p53and p21, significantly higher than that in the control group (p<0.01), were shown in the cytoplasm of the endothelial cells of the vessel wall of the model group. DTD treatment group cell express ion of ICAM-1of p53and p21positive express ion significant ly with less than the model group (p<0.01), and the high-dose group DTD of ICAM-1, p53and p21in suppress ion were s igni ficant with strong in small dose group (p<0.01). The correlation analysis showed that p53, p2l and ICAM-1levels were significantly positively related (p<0.01).In TNF-α induced group ICAM-1, p53and p21protein were significantly higher than the normal control group and blank serum control group (p<0.01). DTD containing serum or PFT-α treatment, TCAM-1, p53and p21expression was significantly decreased (p<0.05), and inhibit gradually increased with the increase in the dose of Dao Tan Tang. The linear correlation analysis showed that p53, p21and ICAM-1mRNA and protein levels were significantly positively correlated (p<0.05). |
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