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Study On Effect Of Total Panax Notoginseng Saponins And Astragalus Membranaceus On Macroangiopathy In Type 2 Diabetes

Posted on:2005-02-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:K Z LiuFull Text:PDF
GTID:1104360125458229Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
With the elevation of living standard, the change of lifestyle and the population becoming aging, the incidence of diabetes mellitus (DM) is increasing year after year. It has become the disease of severely threatening human health. Macroangiopathy including cerebrovascular and coronary artery disease and atherosclerosis is a main cause of deformity and mortality in patients with type 2 diabetes mellitus. Recent studies have shown that the pathological hallmarks of macroangiopathy are the same as atherosclerosis (AS). There are the lipid deposition and vascular extracellular matrix (ECM) remodeling caused by endothelial injury. Matrix metalloproteinase-9 (MMP-9) is one of the Zn2+ dependent proteinases synthesized and secreted by monocytes/macrophages and vascular smooth muscle cell (VSMC) and participates in the degradation of ECM. It plays the key role in regulating the balance of synthesis and degratation of ECM and maintaining the integrity of vascular structure. Even so, the changes of expression and activity of MMP-9 and the relationship between MMP-9 and pathological progress during the development of diabetic macroangiopathy are not clear.The pathogenesis of diabetic macroangiopathy is so complicated that there is no satisfactory prevention and treatment strategy. Recent studies showed that Traditional Chinese Medicine (TCM) has superiotity of multilevel and multifunction regulation compaired with western medicine. Diabetic angiopathy has the same pathological fundation as TCM "blood stasis". Our previous experiments have indicated that Chinese herbs in qi-benefiting and blood-activating to remove blood stasis could treat cardiovascular disease by inducing the apoptosis of VSMC in AS plaque, inhibit VSMC proliferation and abnormal accumulation of ECM and promote blood circulation by regulating the balance of TXA2/PGI2 and tPA/PAI-1. On the basis of previous experiments, the present study explored the relationship between expression and activation of MMP-9 and type 2 diabetic macroangiopathy. At the same time, qi-benefiting and blood-activating TCM, total Panax notoginseng saponins (tPNS) and Astragalus membranaceus (Ast) was applied to investigate the preventive and treatment mechanisms of diabetic macroangiopathy from the whole and molecular level and provide new therapeutic target whereby TCM can treat diabetic macroangiopathy.1 Expression and activity of MMP-9 in arterial wall during the development of type 2 diabetic macroangiopathyMatrix metalloproteinases (MMPs) may play the key role in the occurrence and development of diabetic macroangiopathy by degrading ECM and participating in the reconstruction of matrix in vascular wall. In this study type 2 diabetic macroangiopathy model was established by high-fat diet and a low dose of STZ. Morphological changes of aorta, blood glucose, serum lipids and changes of coagulation and plasmin system were observed in order to explore the relationship between expression and activity of MMP-9 and type 2 diabetic macroangiopathy. The results are as follows:1.1 Morphological changes of aorta: Compared with smooth intima and orderly arranged medial VSMC of aorta in the control rats, the intima thickness was increased, the elastic lamella within the intima was destroyed and the VSMC in the media proliferated, some VSMC in the media migrated to the intima in model rats after 12 weeks of the experiment. The area ratio of injured region to vascular wall in control group and model group was 0.57±0.20% and 1.90±0.34% ( P<0.01), respectively. 1.2 Changes of MMP-9 activity in aorta: SDS-PAGE zymography analysis showed that activity of MMP-9 in model rats was 1.27 times as high as that of control rats, with the prolongaton of diabetes duration and the development of macroangiopathy, its activity increased progressively and was 1.59, 2.15 and 2.72 times of control rats , respectively , at week 4, 8 and 12 after DM.1.3 Changes of MMP-9 expression in aorta: Immunohistochemistry showed that MMP-9 could be detected in aorta of control rats, but th...
Keywords/Search Tags:Matrix metalloproteinase-9, Gene expression, Gene polymorphism, Total Panax notoginseng saponins, Astragalus membranaceus, Atherosclerosis, Type 2 diabetes mellitus
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