The Research Of Anti-atherosclerotic Effects Of 2, 3-dioxoindoline

Objective: 2,3-dioxoindoline (MW147), a nature ocean antibiotic extractedfrom lobster, now has been confirmed existing in natural indigo——a traditional Chinesemedicine and human body as an endogenous active substance. The present study is to study theanti-atherosclerotic action of the 2,3-dioxoindoline and its mechanism in quails atherosclerosismodel established by hyper lipoidal forage.Methods: The model of atherosclerosis in quail was established by hyper lipoidal forage.MW147 was administrated to the quails preventively and therapeutically, the serum and tissuelipid and apolipoprotein were detected, the atherosis plaque in artery, liver and cardiac muscle wasobserved by histopathological methods, the serum superoxide dismutase (SOD), malondiadehyde(MDA), GSH-Px and T-AOC were measured. The medial lethal dose (LD₅₀) of MW147 wasdetermined by one-off intragastfically adiminstration in mice, and the chronic toxicity of MW147were observed by 180 days intragastricaUy adiminstration in rats.Results: MW147 20, 60, 120 mg·kg^-1·d^-1 in preventive and therapeutic administrationsignificantly decreased the serum triglyceride (TG), total cholesterol (TC), low density lipoproteincholesterol (LDL-C) and apolipoprotein B (apoB, P＜0.05,P＜0.01), increased the serum highdensity lipoprotein cholesterol (HDL-C) and apolipoprotein A (apoA, P＜0.05,P＜0.01) ; andMW147 20,60,120 mg·kg^-1·d^-1 in preventive administration decreased TC and TG ofmyocardium, liver and aorta (P＜0.05); compared with model group, the degree of atheroscleroticlesion in aorta and coronary artery and fatty degeneration of liver in MW147 group was reduced(P＜0.05). In therapeutic administration MW147 group, TC and TG in the myocardial, liver andaortic wall were reduced markedly (P＜0.01). The degree of atherosclerotic lesion in myocardiumand coronary artery in MW147 group was decreased. LD₅₀ of MW147 is 1091±359 mg·kg^-1.180 days intragastrically administration of MW147 didn't influence bite and sup action of the rats,and the serum guideline was normal, there was no abnormal pathological finding of the 22 organs.Conclusion: Preventive and therapeutic administration of MW147 showed obvious anti anti-athersclerotic action, the mechanism may be related to the effects of regulation of lipidmet metabolism and antioxidation of MW147.