Interventional effect of emodin on the changes of sphingomylinase activity and ceramide content in experimental rabbit with atherosclerosis / 中国组织工程研究

ABSTRACT

BACKGROUND: It is reported that ceramide signal pathway may play an important role in the apoptosis of vascular endothelial cell and then lead to the progress of atherosclerosis, such as the formation of foam cells and the proliferation of smooth muscular cells.OBJECTIVE: To study the changes of the sphingomylinase activity and ceramide content in aorta of rabbits with experimental atherosclerosis and investigate the regulative effects and mechanism of emodin on them as compared with positive fenofibrate.DESIGN: Completely randomized controlled design.SETTING: Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Science of Sun Yat-sen University.MATERIALS The experiment was completed at the Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Science of Sun Yat-sen University from July to December 2003. Totally 48 New Zealand male rabbits were selected. Forty animal models of atherosclerosis were made with high cholesterol feed, and the other 8 rabbits were selected as the normal controls. Model animals were divided randomly into model group, 5 mg/kg emodin group, 10 mg/kg emodin group, 20 mg/kg emodin group and 25mg/kg fenofibrate group with 8 in each group.METHODS: At the seventh weeks of model duplication, 5 mg/kg, 10 mg/kg and 20 mg/kg emodin were perfused in rabbits of emodin groups respectively, and 25 mg/kg fenofibrate was perfused in rabbits of fenofibrate group. Emodin and fenofibrate were diluted or suspensed with 2 mL saline once per day respectively. Rabbits in normal control group and model group were administrated with the same volume of saline for 4 weeks. The rabbits were raised separately and were fed with 135-150 g food per day.MAIN OUTCOME MEASURES: [1] The area of the lipid plaque in aortal intima; [2] the content of serum TC and TG; [3] SOD activity and MDA content; [4] SMase activity and CER content in aorta.RESULTS: Totally 48 rabbits entered the final analysis. [1] Area of the lipid plaque Area of the lipid plaque was (48.87±15.5) % in the model group, which was larger than that in each emodin group (P ＜ 0.05 or 0.01),especially larger than that in the 10 mg/kg emodin group (22.19±12.9)%while that in the fenofibrate group was similar to that in the model group (P ＞ 0.05). [2] Content of serum TC and TG The anrtal intima of control was smooth. Content of serum TC and TG in each emodin group were similar to those in the model group (P ＞ 0.05), but those in the 25 mg/kg fenofibrate group were lower than those in the model group (P ＜ 0.05). [3]Content of SOD and MDA in plasma SOD activity of rabbits in each emodin group was higher than that in the model group (P ＜ 0.05, P ＜ 0.01),but the MDA activity in the 10 mg/kg and 20 mg/kg emodin group was lower than that in the model group (P ＜ 0.05). The MDA activity in the25 mg/kg fenofibrate group was similar to that in the model group (P ＞ 0.05).[4] Content of SMase and CER Those in the model group were higher than those in the normal control group, but those in the 5, 10 and 20 mg/kg emodin groups were lower than those in the model group; those in the 25 mg/kgfenofibrate group were similar to those in the model group (P ＞ 0.05). [5]Analysis of correlation Content of SMase was in positive relation with blood cholesterol (r=0.542, P ＜ 0.01), in positive relation with blood MDA (r=0.789, P ＞ 0.01), and in negative relation with blood SOD(r=-0.936, P ＞ 0.01); content of CER was in positive relation with blood cholesterol (r=0.433, P ＞ 0.05), in positive relation with blood MDA (r=0.673, P ＞ 0.01), and in negative relation with blood SOD (r=-0.876, P ＞ 0.01).CONCLUSION: The study finds that emodin, despite its insignificant effects on decreasing TG or TC, can protect vascular endothelial cells and reduce the area of lipid-laden plague of aortal intima by antioxidation, inhibition of the sphingomyelinase activity and reduction of the content of ceramide. It is suggested that moderate dosage of emodin employed in the study may be most appropriate to atherosclerosis treatment.