The Correlation Study Of Angiogenesis, Ischemia Hypoxia Level And Traditional-Chinese-Medicine Syndromes On Affected Limbs Of Arteriosclerosis Obliterans

ObjectiveArteriogenesis and angiogenesis play important roles in the compensation mechanism against ischemia and hypoxia, and also are the most focused methods in Arteriosclerosis obliterans therapy. In spite of the uncertain curative effect, therapeutic neovascularization still get his promotion in clinic ASO therapy. To find the appropriate timing of neovascularization intervention, we should trace the compensation procession in ASO, discover the key factors that regulate arteriogenesis and angiogenesis, explore their variation law, master mechanisms of arteriogenesis and angiogenesis in ASO; explore correlation between TCM syndromes and neovascularization in order to choose the proper TCM methods in clinical therapy.58patients were observed, classifying with TCM Syndrome types; and examining ankle-brachial index(ABI) to classifying ischemia transcutaneous Oxygen Pressure (TcPO2) to classify hypoxia; serum factors include HS-CRP,Angll,OX-LDL,HIF-1α,VEGF,and bFGF to evaluate arteriosclerosis obliterans phase and neovascularization level.Methods1. Correlations of TCM syndrome types with TcPO2, ABI, AngI I, HS-CRP, Ox-LDL.Classify58patients with TCM syndrome types into3groups, using TCM syndrome differentiation.15in Cold Coagulation syndrome group,23in Blood Stasis syndrome group,20in Toxicity Accumulation of Damp-Heat syndrome group.Drawn a line from tibia medial nodule to medial malleolus, choose the crosspoint with the lower margin of gastrocnemius muscle as the test point, examining the TcPO2using Radiometer Medical-APS TCM-400minitor.Examining the ankle-brachial index(ABI) using Nicolet Vasoguard P84ABI monitor, monitoring the systolic pressure value of posterior tibial artery and dorsalis pedis artery, choose the higher one, then divided it by the value of brachial artery.Detecting the serum factor’s level with ELISA (double antibody sandwich method), including Angll, HS-CRP, Ox-LDL.2. Correlations of TcPO2and ABI with HIF-1a, VEGF, bFGF expression level in different TCM syndrome types.Reclassify patients according to the statistical distribution of ischemia and hypoxia level in TCM syndromes.Reclassify patients with TcPO2into3groups.23in low hypoxia group,21in medium hypoxia group,14in high hypoxia group.Reclassify patients with ABI into2groups.33in medium ischemia group,25in high ischemia group.Detecting the serum factor’s level with ELISA (double antibody sandwich method), including HIF-1a, VEGF, bFGF.3. Correlations of TCM syndrome types with HIF-1a,VEGF and bFGF.Statistical analysis was based on the results of Testl and Test2.Results1. Correlations of TCM syndrome types with TcPO2, ABI, AngII, HS-CRP, Ox-LDL.Cold Coagulation syndrome has the lowest ischemia level, Blood Stasis in medium, and Toxicity Accumulation of Damp-Heat the highest.Cold Coagulation syndrome has the lowest hypoxia level; No statistical difference was detected between Blood stasis and Toxicity Accumulation syndrome.No statistical difference was detected between these groups on Angll and Ox-LDL.Cold Coagulation syndrome has the lowest HS-CRP level. No statistical difference was detected between Blood stasis and Toxicity Accumulation of Damp-Heat syndrome.2. Correlations of TcPO2and ABI with HIF-1a, VEGF, bFGF expression level in different TCM syndrome types.No statistical difference was detected between medium and high ischemia groups on TcP02, HIF-1a, VEGF and bFGF.Significant differences can be seen on both medium hypoxia group and high hypoxia group compared with low hypoxia group, in ABI, HIF-1a and VEGF. ABI decreased significantly, and HIF-1a, VEGF increased significantly. No statistical difference was detected between medium hypoxia group and high hypoxia group on these factors. The value of bFGF increased significantly in high hypoxia group compared with low hypoxia group. No statistical difference were detected between low hypoxia group and medium hypoxia group, as well as between medium hypoxia group and high hypoxia group3. Correlations of TCM syndrome types with HIF-1α,VEGF and bFGF. Cold Coagulation syndrome has the highest bFGF level. No statistical difference was detected between different TCM syndromes on HIF-1α and VEGF.Conclusions1. Correlations can be found between TCM syndromes with ischemia and hypoxia level. Cold Coagulation syndrome has the lowest ischemia level, Blood Stasis in medium, and Toxicity Accumulation of Damp-Heat the highest. Cold Coagulation syndrome has the lowest hypoxia level; No statistical difference was detected between Blood stasis and Toxicity Accumulation of Damp-Heat syndrome.2. Cold Coagulation syndrome has the lowest inflammation and tissue damage level. No other statistical difference was detected between TCM syndromes on pro-atherosclerosis factors.3. No significant differences can be seen between the TCM syndromes on angiogenesis level.4. In the medium and high ischemia phase, no correlations can be found between ischemia level with hypoxia level and angiogenesis factor.5. In low-medium hypoxia phase, the level of angiogenesis increased with hypoxia. In medium-high hypoxia phase, it remained in high level, and not relevant with hypoxia.6. No time-synchronization was found between hypoxia and ischemia in ASO progress. Due to the compensation mechanism of neovascularization, hypoxia process is lagging behind ischemia process.7. Angiogenesis is the major self-compensation method in both medium hypoxia and high hypoxia phase. The mechanism of Angiogenesis promoting tissue O2supply could be familiar with the "Dilution" process. Insufficient blood supply in local arterial for the capillary sprouting is mostly responsible for the failure of angiogenesis compensation. The angiogenesis spouting could be the major promoting factor in tissue hypoxia.