Studies On The Effects Of Tibolone On Experimental Atherosclerosis Model In Rabbits

Objective: The purpose of this study was to investigate the effects of tibolone on the atherosclerosis of ovariectomized female rabbits.Methods: Sixty female New Zealand White rabbits, 7-9 months, all the sixty rabbits were fed with standard feed for three weeks. Then they were randomized into six groups: PI-O group, PI-N group, CTRL group, TIB group, PRE group, SIM group. The rabbits of PI-O group, CTRL group, TIB group, PRE group, SIM group were ovariectomized. Then the rabbits of CTRL group were fed with standard feed, the rabbits of other groups were fed with atherogenic diet (0.4% cholesterol, 3.75% coconut oil and 3.75% peanut oil in standard rabbit chow diet), at the same time, the rabbits of TIB group were fed with 2.5mg tibolone every day, the rabbits of PRE group were fed with 0.625mg premarin every day, the rabbits of SIM group were fed with 20mg simvastatin every day, the rabbits of PI-O group, PI-N group and CTRL group were fed with 2.5mg amylum every day. All the rabbits were housed according to the Animal Welfare Act specifications. This portion of the study lasted 12 weeks. At the end of the 3, 7, 12, 15 weeks, the concentration of estradiol in the serum of the rabbits was measured. The concentration of fat in the serum of the rabbits was measured at the end of the 15 weeks. At the end of the experiment, the abdomen and chest of the rabbits were opened, and the livers, kidneys, hearts, carotid arteries, the arch of aortas, thoracic aortas and abdominal aortas were harvested. All surgical procedures were performed by sterile techniques. The arch of aortas were dissected, coded and prepared for transmission electron microscope according to regular methods. Other tiissues were coded, immersed in 10% neutral buffered formalin and were allowed to be fixed overnight at 4℃, then they were routinely embedded in paraffin, and tissue sections were proceeded for hematoxylin and eosin staining. The thoracic aortas were also prepared for general sodan IV staining, the plaque appeared red after the treatment, the area of the plaque was measured with an automated computerized image analyzer. The thickess of the carotid intima was also measured with an automated computerized image analyzer. The slices of the thoracic aortas, abdominal aortas, livers, kidneys and hearts were observed with optical microscope after hematoxylin and eosin staining. The slices of the arch of aortas were observed with transmission electron microscope.Results: Except the CTRL group, lipide stripe and atherosclerosis plaque were found in other groups. Compared to the PI-O group, PI-N group and PRE group, the area of atherosclerosis plaque of the TIB group and SIM group were mild, the thickess of intima of the TIB group and SIM group changed indistinctively. Compared to the PI-O group and PI-N group, the concentration of triglyceride and low density lipoprotein-cholesterol in the serum of TIB group decreased evidently, the concentration of triglyceride, total cholesterol, low density lipoprotein-cholesterol and apoB in the serum of SIM group decreased evidently. The pathological changes of liver, kidney and heart of the TIB group and SIM group were unconspicuous, and the pathological changes of liver, kidney and heart of the PRE groupwere lighter than that of the the PI-N group and PI-0 group. The pathological changes of the arch of aortas, thoracic aortas and abdominal aortas of the TIB group and SIM group were also very mild. Conclusions: Tibolone has remarkable effects on atherosclerosis of ovariectomized female rabbits.