A Empirical Study On How To Induce An Animal Model Of Isolated Systolic Hypertension And Early Intervention

Objective: To generate an animal model of isolated systolic hypertension in rat and investigate whether doxycycline, a matrix metalloproteinase inhibitor, could interfere in the formation of isolated systolic hypertension so as to provide a new idea for isolated systolic hypertension deference even therapy.Methods: 8 weeks age-matched male Wistar rats were selected to study, all 30 the rats were randomly divided into intervention group of doxycycline(n=10), pure modeling group(n=10) and blank control group(n=10). Medial elastocalcinosis were induced by warfarin and vitamin K1. 4 weeks and 8 weeks later, blood pressure and left intraventricular pressure were measured by right carotid arterial cannulation; and the segments from each aorta was processed for histological analysis, immunohistochemistry, and Calcilium analysis. Rats in intervention group of doxycycline were done with intragastric administration at the same time to investigate whether doxycycline could interfere in the formation of isolated systolic hypertension. Elatic/collagen ratio and calcification degree were measured according to different coloration methods. MMP-9 was explored by immunohistochemistry and western-bloting. Aortic calcilium contents were calculated in each group with atom-spectrum.Results: The blood pressures in the pure modeling group were higher than in the intervention group of doxycycline (p<0.05) and blank control group (p<0.01); the blood pressures in the intervention group of doxycycline were also increased compared with the blank control group (p<0.05), but the mean left intraventricular pressure donot show an obviously change in the study group. The blood pressure of ISH animal changed with morphological aspect of each aorta, which was associated with extensive arterial medial elastocalcinosis, and the elastic lamellae was flatten, accompanied loss of the natural waviness. The degree of Medial elastocalcinosis was decreased in the intervention group of doxycycline, which followed the natural wavy aspect of the elastic lamellae. calcilium contents were increased in the pure modeling group compared with the intervention group of doxycycline (p<0.05)and the blank control group (p<0.01). Western-bloting analysis showed that protein synthesis of MMP-9 in the pure modeling group increased obviously as compared with that of the blank control group while MMP-9 activity was inhibited in the intervention group of doxycycline.Conclusion: The presence of MMP-9 is required for elastin degeneration and calcification in the aortic elastic fibers, and doxycycline may prevent the formation of aortic stiffening and isolated systolic hypertension by inhibiting MMP-9 activity in vessel.