| Matrine is the main active ingredient in leguminous plant of sophora alopecuroides. With the researching of matrine, found that the matrine has a lot of works in hypotensive, antitumor, resisting arrhythmia, resisting lack of oxygen, dilate blood vessels, prevention of myocardial fibrosis, and so on. Nitric oxide was found in the 1980 s, which can dilate blood vessels in the cardiovascular system. Nitric oxide has obvious curative effect in the prevention and treatment of acute myocardial ischemia and acute heart failure. Nitric oxide-drugs combined the existed drugs with nitric oxide donor through different connection groups. Now, the research has showed that Nitric oxide-drugs can release nitric oxide and drugs which have a high effect and low side effect.Objectives 1 Based on the characteristics of matrine structure,preparing different types of nitric oxide donor compounds with organic nitrate ester as nitric oxide donor.2 Investigating the protective effect of the NO donor-marine derivatives on rats with isoproterenol(ISO)-induced chronic heart failure.Methods: 1 Combined matrine with chloride-organic nitrate ester, which can preparation of nitric oxide donor –matrine. Combined matrine with organic acid nitrate ester can received the salt of nitric oxide donor- matrine.2 myocardial ischemia was induced in rats by subcutaneous injection of ISO(5mg·kg-1) for seven consecutive days. The inhibition of histopathological injuries in the rat myocardial tissues was observed under the exposure to different doses of matrine.The serum levels of NO and ADMA were determined by enzyme-linked immunosorbent assays and biochemical methods.Results 1 A total of 8 compounds were synthesized: 12-N-(3-nitrooxymethylbenzoate) matrine acid, 12-N-(4-nitrooxymethylbenzoate) matrine acid, 12-N-(nitroxyacetyl) matrine acid, 12-N-(n- nitroxybutyryl) matrine acid,3-(nitrooxymethyl)benzoic acid matrine, 4-(nitrooxymethyl)benzoic acid matrine, Nitrooxyacetic acid matrine, n-Nitrooxybutyric aci matrine.2 The histopathological study showed that NO- matrine attenuated myocardial necrosis, infiltration of inflammatory cells, interstitial edema and other abnormalities in rats with ISO-induced chronic heart failure. Compared with the control group, ISO-treated rats showed that the serum NO level was reduced and the serum ADMA level was elevated. Compared with the matrine group, the serum NO level was increased.Conclusions 1 Based on the characteristics of matrine structure, this study designed and synthesized amides and ionic nitric oxide donor –matrine. 2 3-(nitrooxymethyl)benzoic acid matrine has a high effect on against myocardial ischemia. |
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