| ForewordAbdominal aortic aneurysm(AAA) has been a common diaease in clinic, and with ageing of population, patients of AAA become more and more. Once disrupted, it would threat to life. With the development of modern medicine, AAA has can be cured, but the pathogenesy of AAA is not completely clear, which directly influence the effect of prevention and cure to AAA in earlier period.It has been reported that matrix metalloproteinases,artherosclerosis, artery medionecrosis,copper deficiency and some genetic predisposition has correlation with AAA. AAA is consequence of artery wall dilating, which result from complex action of age, environment and gene.Clinical epidemiology study indicates that the there are obvious difference between men and women on incidences of AAA, and the former is 4～6 times of the later. While the diminished risk of AAA development is lost in women after menopause. It suggests that estrogen may play a protective role in AAA development.Estrogen is one of hormones with extensive regulation effect, and its effect to immune system attract many investigators' attention. It is observed in clinic that estrogen has close correlation with some autoimmune disease or mammary cancer, and the substitutive therapy of estrogen can cure some disease, which suggest that estrogen may play some roles in maintenance and regulation of immune system.Many studies in AAA evolution have used a rat or mouse model with porcine pancreatic elastase perfusion of the infrarenal aorta. This model causes an initial influx of macrophages leading to destruction and remodeling of the aorta wall matrix, and subsequent aneurysm development. Importantly, nearly all previous studies have been performed using male rodents. To date, the influence of gender on experomental AAA formation has received little attention. Further more, although estrogen is known to affect collagen and elastin matrix remodeling in rats, its roles in AAA formation has not been studied. This investigation is designed to determine the role of estrogen in experimental AAA formation, which would provid a new clue on the cause,prevention and cure of AAA. Our work includs three parts listed below.Part oneObjectiveTo investigate the gender differences in the formation and development of experimental Abdominal Aortic Aneurysm by comparing the MMP-2 and MMP-9 mRNA and protein expression in the aneurysms tissue.MethodsSegmental elastase or saline perfusion of infrarenal aorta was performed in Male and female rats (10 rats per group). At 14 days, aortas were harvested for immunohistochemistry, real-time RT-PCR to detect the protein and mRNA expression of MMP-2 and MMP-9.Results aneurysm dilatation rate of female and male rats of elastase perfusion were (103.84±5.86)%和(178.72±11.06)% respectively(P＜0.01). Their relative expression quantities of MMP-2 mRNA were 0.02±0.01 and 0.46±0.25 respectively (P＜0.01) and that of MMP-9 mRNA were 0.42±0.24 and 4.30±2.87 respectively (P＜0.01). MMP-2 protein expression rate of male and female rats were (22.50±5.15)% and (46.45±9.38)% respectively (P＜0.01) and that of MMP-9 were (26.44±2.41)% and (42.50±3.22)% respectively (P＜0.01). aneurysm diameter of female and male rats of saline perfusion weren't significant alter.ConclusionsIn AAA formation and development, MMP-2 and MMP-9 mRNA and protein expression of female rat were all obviously lower than those of male rats, which lead to the obvious difference of aneurysms dilatation rate. It suggests that female rats inhibit the AAA formation as compared to Male rats.Part twoObjectiveTo investigate the role and the mechanism of estrogen deficiency in the formation and development of abdominal aortic aneurysm of Female rats.MethodsFemale Wister rats were divided into experiment group and control group randomly(5 rats per group). Rats in experiment group were ovariectomized and those of control group were sham-operated. Elastase perfusion of the infrarenal aorta was performed in rats. At 14 days, estrogen was detected by radioimmunoassay and aortas were harvested for immunohistochemistry, real-time RT-PCR to detect the protein and mRNA expression of MMP-2 and MMP-9.ResultsExperimental group showed a lower estrogen level than control group, P＜0.01. Aneurysms dilatation rate of experiment group and control group were (160.52±18.38)% and (101.30±6.73)% respectively (P＜0.01). Their relative expression quantities of MMP-2 mRNA were 0.13±0.07 and 0.02±0.01 respectively (P＜0.01) and that of MMP-9 mRNA were 1.50±0.43 and 0.33±0.11 respectively (P＜0.01). MMP-2 expression rate of experiment group and control group were (48.51±9.63)% and (25.33±3.15)% respectively (P＜0.01) and that of MMP-9 were (46.46±5.91)% and (24.78±2.30)% respectively (P＜0.01).ConclusionsIn AAA development of Female rats, estrogen deficiency may promote the AAA formation by enhance MMP-2 and MMP-9's expression of mRNA and protein and inflammatory cell infiltrate.Part threeObjective To investigate the role of estrogen in the formation and development of Abdominal Aortic Aneurysm of male rats.MethodsMale Wister rats were divided into experiment group and control group randomly (5 rats per group). Rats in experiment group were injected with estrogen and those in control group were injected with NS regularly. Segmental elastase perfusion of the infrarenal aorta was performed in rats. At 14 days, estrogen was detected by radioimmunoassay and aortas were harvested for immunohistochemistry, real-time RT-PCR to detect the expression of MMP-2 and MMP-9.ResultsExperimental group showed a higher estrogen level than control group, P＜0.01. Aneurysms dilatation rate of experiment group and control group were (103.30±4.32)% and (172.30±13.26)% respectively (P＜0.01). Their relative expression quantities of MMP-2 mRNA were 0.07±0.04 and 0.22±0.07 respectively (P＜0.01) and that of MMP-9 mRNA were 1.41±0.70 and 7.43±2.82 respectively (P＜0.01). MMP-2 protein expression rate of experiment group and control group were (22.22±3.01)% and (49.66±11.94)% respectively (P＜0.01) and that of MMP-9 were (23.04±2.22)% and (45.01±10.22)% respectively (P＜0.01).ConclusionsIn AAA formation and development of male rats, MMP-2 and MMP-9 mRNA and protein expression of experiment group were all obviously lower than those of control group, which lead to the obvious difference of aneurysms dilatation rate. It suggests that estrogen may inhibit the AAA formation and development by reducing MMP-2 and MMP-9 mRNA and protein expression and inflammatory cell infiltrate.
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