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The Interferential Effect Of Simvastatin On Osteoporosis In Ovariectomized Rats

Posted on:2009-05-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y C GuoFull Text:PDF
GTID:2144360245484888Subject:Surgery
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Objective : Postmenopausal Osteoporosis is a common disease of the middle and old-aged women, with the aggravation of aged population of world, it has gradually become the one of major disease, which does harm to the health of the middle and old-aged women , it has badly affected the life status and quality of the middle and old-aged women. In the research of the postmenopausal osteoporosis, the currently clinical treatment of osteoporosis is too limited , the therapeutic efficacy is still not satisfactory and it also can brings some side effects. Therefore, Clinical intervention study on osteoporosis still is a clinical important problem urgently to be resolved. In study of postmenopausal osteoporosis, ovariectomy induced osteoporosis in rats could be better modeled with the postmenopausal osteoporosis of the middle and old aged women makes it possible that the rats become the most common animal models so far to now . This study is to create the model of osteoporosis of ovariectomized rats, and to measure the two indexes of the bone strength and BMD combining with the histological analysis so as to evaluate the intervential effect of simvastatin on ovariectomized rats, in order to supply scientific therapy and prevention evidence for osteoporosis in ovariectomized rats.Methods: Sixty 3-month-old femal SD rats with weight (212.3±2.7g) were randomly divided into the three groups : the control group(SHAM 20 ),the ovariectomized rats group (OVX 20) and the simvastatin intervention group (SIM 20); the sham-ovariectomized group(SHAM) treated as control group . After anesthesia, the ovaries of the ovariectomized group and the simvastatin intervention group were removed bilaterally to establish osteoporosis model. In the control group (SHAM) only the fatty tissues surround of ovaries is removed, no antibiotics were used in this study;the ovariectomized (OVX) group and the simvastatin intervention group (SIM)were orally injected simvastatin into the stomach from the first day(5mg/kg·d) on. The sham-operation (SHAM) rats as normal control group were gavaged with equivalent normal saline through mouth. Weight them every week , change the injection dose according to the weight . After anesthesia measure the total bone density 12 weeks later to identify that the osteoporosis model is established , the rats were executed immediately through exsanguination after the BMD examination and both femurs were removed , the left femur were surrounded by normal saline gauze , bone biomechanical properties( stress ,elastic modulus ) were determined by the three point bending test, the right femurs were fixed in the 10% neutral formalin liquid left for the histological slice and microscopic histological observation , the femoral neck trabecula change (width and relative area) was analyzed by the photograph analysis system. Treating BMP/weight×100 in both OVX and SIM group as the correction value .Experiment datas were showed by mean±std( x±s)and the median express the mean and the quartiles expressed the range of the mean in the skew distribution data ,all that was calculated by spss10.0 software, single factor analysis of variance was adopted in inter-group comparison, and the means comparison between multi-sample was done by the q-test, and nonparametric test was done in heterogeneity of variance or skew distribution data (α=0.05) .Results: 12 Weeks after ovariectomy the trial rats (OVX) the total BMD(0.230±0.003) contrast to control group (SHAM) (0.245±0.002)were decreased significantly (P<0.01) , the model is established ; the ovariectomized group's total BMD (0.230±0.003) was lower than that of the simvastatin group (0.242±0.001); the simvastatin intervention group's total BMD was lower than that of (SHAM) control group' s (0.245±0.002) (P<0.01) ;the simvastatin intervention group's the total corrected BMD (0.0093<0.002>)was higher than that of ovariectomized group's (0.0079<0.001>) (P<0.01) .And significant difference was obtained in the bone strength (maximum stress, elastic modulus) in the 3 trial groups(P<0.01), the ovariectomized (OVX) group' max stress and elastic modulus(128.9±2.0,2120.5±1.7) is lower significantly than that of the control group (SHAM) and the simvastatin intervention group (SIM) (175.7±2.7,3321.3±0.4;172.2±1.9,2918.0±2.0) , simvastatin intervention group ' max stress and elastic modulus is smaller significantly than that of control group(P<0.01) ; Contrast to the control group(SHAM)and simvastatin intervention group(SIM)(51.02±0.49,<18.06±0.01>%;51.73±0.38,<24.03±0.03>%), the femoral neck bone trabecula of the ovariectomiz-ed group rats became thinner and the relative volume become smaller (27.79±0.60,<9.46±0.03>%) (P<0.01). The femoral neck bone trabecula of simvastatin intervention group became wider and relative volume become larger than the sham group (P<0.01).Conclusion: (1) The model of ovariectomized osteoporosis was established after 12 weeks of ovariectomy on 3-month old rats. (2)The total bone density ,the femur bone strength (maximum stress and elastic modulus) of The osteoporotic rats was significantly decreased after ovariectomy , the femoral neck bone trabecula became thinner and relative volume become smaller. The total bone density, the femur strength ( maximum stress, elastic modulus ) of the rats were enhanced and the relative area and the the average width were increased significantly by simvastatin administation ,It has improved effectively the bone trabecula microstructure. (3) It is proved to be feasible to use simvastatin to intervent the osteoporosis in ovariectomized rats.
Keywords/Search Tags:ovariectomy, osteoporosis, BMD, bone strength, histology, simvastatin
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