Application of spermidine in preparation of aortic aneurysm treatment drug
A technology for aortic aneurysm and abdominal aortic aneurysm, which is applied in the direction of pharmaceutical formulations, drug combinations, and medical preparations containing active ingredients. High sex, clear toxicology and pharmacology effect
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Embodiment 1
[0025] Model establishment: mouse abdominal aortic aneurysm induced by trypsin infusion can simulate the pathophysiological mechanism of human abdominal aortic aneurysm formation, and can also reflect extracellular matrix degradation, smooth muscle cell apoptosis, inflammatory response, oxidative stress and other lesions, the postoperative survival rate is about 90%, and the tumor formation rate after survival is 100%. It is a widely recognized classic abdominal aortic aneurysm model.
[0026] We randomly divided 40 male C57 mice aged 8-10 weeks into two groups, 20 in each group. The control group had a normal diet, and the experimental group added spermidine (concentration 3 mmol / L) to their drinking water. The abdominal aortic aneurysm was formed on the 14th day after modeling, and the diameter of the aneurysm was measured by laparotomy and compared with the initial diameter ( figure 1 ), defined as neoplasia when the expansion was more than 50%. After measuring the aneurys...
Embodiment 2
[0028] Histopathological evaluation
[0029] In order to further evaluate the therapeutic level of spermidine, we used section staining to evaluate the degree of vascular lesions at the histopathological level, and then evaluated the therapeutic effect of spermidine.
[0030] After tumor formation in the two groups of mice, we took aneurysm specimens for paraffin-embedded and fixed sections, and used staining techniques for histopathological evaluation. We used EVG staining to observe the staining of elastic fibers in blood vessels, Masson staining to observe the staining of collagen fibers and muscle fibers in blood vessels, and SMA staining to observe the staining of vascular smooth muscle ( Figure 4 ). The experimental results show that spermidine can significantly improve the degradation of elastic fibers, the destruction of muscle fibers and collagen fibers, and the reduction of smooth muscle cells in abdominal aortic aneurysms. It was suggested that spermidine improve...
Embodiment 3
[0033] Flow Cytometry Evaluation
[0034] In order to further verify the effect of spermidine on the infiltration of inflammatory cells in aneurysm tissue, we used flow cytometry to evaluate the proportion of inflammatory cells in aortic tissue. We first digested the aortic tissue into single suspension cells with digestive enzymes, then labeled the corresponding cells with fluorescent antibodies, and finally analyzed and quantified them by flow cytometry. We found that in the spermidine-treated group, the proportion of leukocytes in the aneurysm tissue was significantly reduced (CD45 + )(P Image 6 ), suggesting that spermidine reduced inflammatory cell infiltration in abdominal aortic aneurysms.
[0035] Since inflammatory monocytes in mouse blood are the precursors of inflammatory cells such as monocytes and macrophages in abdominal aortic aneurysms, we also evaluated circulating inflammatory monocytes in mice and found that sub Spermine reduces the levels of circulating i...
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