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Studies On Tibolone And The Expression Of Related Receptors In Atherosclerotic Rabbits

Posted on:2006-03-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y L CuiFull Text:PDF
GTID:1104360152492428Subject:Clinical Veterinary Medicine
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Atherosclerosis is the pathology of ischemic cardiovascular disease. The morbidity increased with age and the morbidity of cardiovascular disease in postmenopausal women is four times of that in pre-menopausal women. Data from studies demonstrated that estrogen has protective effects on cardiovascular system, the low level estrogen is the main source of higher morbidity. Livial is the only synthetic steroid of tissue-specific used for menopause syndrome, it has been used widely for few side effects, and furthermore, it's anti- atherosclerosis effects and molecular mechanism is not definite.Rabbit used for atherosclerotic model has more advantage for intrinsic physiology character. In the present study, we replicated the AS model of postmenopausal women with ovariectomized rabbit and high cholesterol feed, the CEE (premarin) and simvastatin were used as comparison, 60 rabbits were divided into 6 groups randomly. The AS plaque areas of Livial group and others treatments were analyzed with Imagine Analysis System, furthermore, the paraffin slices of artery were observed with microscope. The study showed: the plaque areas of ovariectomized rabbits with high cholesterol feed (group C) and sham operation rabbits with high cholesterol feed (group SC) was 0. 75 ±0. 24 and 0. 56 ±0. 27 separately; the plaque areas of ovariotomied rabbits with normal feed (group N) was about 0; that of ovariotomied rabbits with high cholesterol feed plus Livial (group TIB, 2.5mg/day) was 0. 10+ 0.02; the plaque areas of ovariectomized rabbits with high cholesterol feed plus premarin (group PRE) or simvastatin (group SIM) was 0. 51 ±0. 28 and 0.09±0.08 respectively. The results indicated that Livial can reduce the development of AS for the scarcity of estrogen, no significant difference was observed compared with that of simvastatin, premarin can reduce the AS plaque area slightly. The present results provided reference data for drug use.We investigated the expression of ERa in artery, heart, liver and kidney with immunohistochemistry. The ERa expressed in the nuclei of VSMC and ETC abundantly, yet no expression was observed in the studied parenchymal organs. The results showed that estrogen can increased the expression of ERa in VSMC , the H-Score of group C, SC, N, TIB, PRE, SIM was 26.3±5.1 , 52.7±11.6 , 43.4±15.2, 87.1±18.2, 46.9±11.3, 29.5±9.4 separately. The results indicates that Livial increased the expression of ERa in artery, the expression of ERa in group SC was not decrease, simvastatin reduced the progress of AS and has no effect on the expression of ERa.In order to investigate the anti-atherosclerotic mechanism of Livial, the expression of ERa and LDLR mRNA in heart and liver were analyzed by real-time quantitive RT-PCR. According to experimental design and intention the relative quantitive method was used with β-actin as a keeping house gene. The results showed: Livial increased the level of of ERa mRNA in heart and liver, simvastatin has no effect on the expression of ERa mRNA in heart and liver, premarin slightly increased the expression of ERa mRNA in heart and liver. The analysis for the expression of LDLR mRNA in heart and liver showed: Livial and premarin increased the expression of LDLR mRNA , simvastatin has no significant effect on the the expression of LDLR mRNA in heart and liver. We conclude that Livialhas the function of anti-atherosclerosis by increasing the level of ERa mRNA, and Livial also has effect on the expression of LDLR mRNA; estrogen preparations have different mechanism on organism.
Keywords/Search Tags:Atherosclerosis, Llivial, Rabbit, Estrogen receptor, Low density lipoprotein receptor
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