| With the developing of society as well as the medicine technology, the expectation of life of Chinese is increasing day by day and the percentage of the aged is increasing accordingly, which means that we are stepping into an aging society. Therefore, the study of vascular aging, the structural and/or functional changes of cardiovascular system with aging, is of great importance. It has been found out that there is an interaction between vascular aging and cardiovascular diseases, which has a harmful effect on the pathogenesis. Besides, adventitia as well as adventitial fibroblasts (AF) is becoming a new breakthrough point of the study of vascular aging for its role in flexibility keeping by secreting extracellular matrix such as collagen.In the preparatory works, the mechanism of delaying senility with traditional Chinese medicine of tonifying qi and activating blood has been studied from endothelial cell and smooth muscle cell aspect. Based on those, this study researched vascular aging and the treatment with traditional Chinese medicine from the adventitial aspect following the way of angiotensin Ⅱ (Ang Ⅱ), nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase component as p47phox and reactive oxygen species(ROS).Besides, an investigation was made to identify the patterns of syndrome of vascular aging. It is expected that this study could provide a scientific basis for the subject of vascular aging delaying and the corresponding treatment with traditional Chinese medicine.This study is divided into three parts:literature review, basic research and clinical research.1. Literature reviewBy sorting and summing up the literatures of adventitia and AF, the effects of adventitia and AF in the vascular diseases were summarized.2. Basic research This part includes three basic experiments.Experiment Ⅰ:Experimental Study on Traditional Chinese Medicine of Tonifying Qi and Activating Blood Delaying Vascular Aging of Senescent RatObjective:To explore the structural and functional changes of vascular in senescent rat as well as the therapeutic effect of traditional Chinese medicine(extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong) Methods:The model of natural aging was built, and all rats were divided into6groups as aging-model group, young control group, traditional Chinese medicine high-dose group, traditional Chinese medicine medium-dose, traditional Chinese medicine low-dose group, and Losartan control group. After15-week intervention the following indexes were observed with corresponding methods:memory acquisition and preservation ability by Morris water maze, morphological changes of aorta by HE and picrosirius red stainings, adventitial ultra-structure by scanning electron microscopy, the plasma renin activity and the content of rennin AngⅡ by radio immunoassay, the content of hydroxyproline by biochemical analysis, the levels of anti-endogenous superoxide anion (O2-) by biochemical analysis, the content of MMP-1and TIMP-1with enzyme linked immunosorbent assay(ELISA), mRNA and protein expression of NADPH oxidase p47phox, type1and2receptor (AT1R, AT2R)of angiotensin by real-time polymerase chain reaction(RT-PCR) and Western Bloting.Results:Compared with young control group, the aging model showed characteristics as following:increased thickness of adventitia, hyperplasia of AF, abnormality of collagen, abnormality of MMP-1/TIMP-1, increased content of AngⅡ, hydroxyproline and O2-of adventitia, decreased expression of mRNA and protein of AT1R, increased expression of mRNA and protein of AT2R and p47phox, declined ability of memory acquisition and preservation. And the Traditional Chinese Medicine could improve the adventitial morphology changes, inhibit hyperplasia of AF, improve the abnormality of collagen as well as MMP-1/TIMP-1,decrease content of AngⅡ, hydroxyproline and O2-of adventitia, increase the expression of mRNA and protein of AT1R and AT2R, decrease the expression of mRNA and protein of p47phox, improve the ability of memory acquisition and preservation of rats.Conclusion:Remodeling was showed in adventitia of aged vascular, which may happen following the way of AngⅡ, NADPH oxidase p47phox and ROS; The extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong could delaying vascular aging possibly by its interference with multitarget, such as AngⅡ and AT1R of adventitia.Experiment Ⅱ:Experimental Study on Traditional Chinese Medicine of Tonifying Qi and Activating Blood Delaying AF Replicative SenescenceObjective:To observe the patholological changes of replicative senescence in AF, as well as the therapeutic effect of traditional Chinese medicine(extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong)Methods:AFs were induced to aging by generation culvitation in order to make models. The AFs in vitro were divided into5groups:the control group, the cell-senescence untreated group, traditional Chinese medicine high-dose group, and traditional Chinese medicine low-dose group, Vitamin E control group. After intervention, the following indexes were observed with the corresponding methods: changes of aging by senescence-associated-β-galactosidase(SA-β-gal) staining method, status of hyperplasy by MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay, mitotic cycle by flow cytometer, the content of MMP-1and TIMP-1by immunocytochemical method, the levels of O2-by biochemical analysis, the content of type Ⅰ collagen and type Ⅲcollagen by ELISA, mRNA and protein expression of NADPH oxidase p47phox, type1and2receptor (AT1R, AT2R)of angiotensin by real-time polymerase chain reaction(RT-PCR) and Western Bloting.Results:Ageing AF showed characteristics as following:the increased expression of SA-β-gal staining, increase the percentage of AF in S Phase, increased content of type Ⅰ collagen while decreased type Ⅲ collagen, increased expression of TIMP-1while decreased of MMP-1, increased fluorescence intensity of ROS in cells, increased production of O2-, increased expression of mRNA and protein of p47phox and AT2R, decreased expression of mRNA and protein of AT1R. The traditional Chinese medicine could decrease the positive expression of SA-β-gal staining, increase the percentage of AF in G1Phase, improve the abnormality of collagen, increase the expression of type Ⅰ collagen and decrease type Ⅲcollagen, decrease fluorescence intensity of ROS in cells, decrease production of O2-increase the expression of mRNA and protein of AT1R and AT2R, decrease the expression of mRNA and protein of p47phoxConclusion:The extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong could improve AF replicative senescence possibly by the way of NADPH oxidase p47phox and ROS.Experiment Ⅲ:Experimental Study on Traditional Chinese Medicine of Tonifying Qi and Activating Blood improving proliferation, collagenation abnormality, et al of AF induced by Ang ⅡObjective:To observe the patholological changes of AF induced by Ang Ⅱ, as well as the therapeutic effect of traditional Chinese medicine(extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong)Methods:AFs were induced by AngⅡ in order to make models. The cultured AFs in vitro were divided into5groups:the control group, Ang Ⅱ induced group, traditional Chinese medicine high-dose group, traditional Chinese medicine low-dose group, and valsartan control group. After intervention, the following indexes were observed with the corresponding methods:changes of aging by SA-β-gal staining method, status of hyperplasy by MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay, mitotic cycle by flow cytometer, the content of MMP-1and TIMP-1by immunocytochemical method, the levels of O2-by biochemical analysis, the content of type Ⅰ collagen and type Ⅲcollagen by ELISA, mRNA and protein expression of NADPH oxidase p47phox, type1and2receptor (AT1R, AT2R)of angiotensin by real-time polymerase chain reaction(RT-PCR) and Western Bloting.Results:The AF induced by Ang Ⅱ showed characteristics as following:the increased expression of SA-β-gal staining, increase the percentage of AF in S Phase, increased content of type I collagen while decreased type Ⅲ collagen, increased expression of TIMP-1while decreased of MMP-1, increased fluorescence intensity of ROS in cells, increased production of O2-, increased expression of mRNA and protein of p47phox and AT2R, decreased expression of mRNA and protein of AT1R. The traditional Chinese medicine could decrease the positive expression of SA-β-gal staining, increase the percentage of AF in G1Phase, improve the abnormality of collagen, increase the expression of type Ⅰ collagen and decrease type Ⅲ collagen, decrease fluorescence intensity of ROS in cells, decrease production of O2-, increase the expression of mRNA and protein of AT1R and AT2R, decrease the expression of mRNA and protein of p47phox.Conclusion:The extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chanxiong could improve AF induced by AngⅡ possibly by the way of AngⅡ, NADPH oxidase p47phox and ROS.3. Clinical Research:Study on syndrome types of vascular agingObjective:To investigate the patterns of syndrome in the population with vascular agingMethods:231patients with essential hypertension were selected as research object. After physical examinations of both modern medicine and traditional Chinese medicine, the results relating vascular aging were analyzed by the statistics methods of cluster analysis and principal component analysis.Results:The main patterns of syndrome are the syndrome of blood stasis, the syndrome of deficiency of qi, and the syndrome of yin asthenia of the patients with essential hypertension as well as vascular aging; The main patterns of syndrome are the syndrome of phlegm, the syndrome of blood stasis, and the syndrome of deficiency of qi of the patients with essential hypertension, vascular aging and atherosclerosis.Conclusion:The syndrome of blood stasis and the syndrome of deficiency of qi, are the main patterns of syndrome of vascular aging. |
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