目的 研究苦參堿對阿霉素誘導大鼠心肌損傷的保護作用及其機制。方法 SD大鼠隨機分為對照組、模型組和苦參堿25、50、100mg/kg組,每組各20只。模型組大鼠ip注射用阿霉素2.5mg/kg,1次/周,連續(xù)給藥6周,累積劑量15mg/kg,建立心肌損傷模型。對照組ip等量生理鹽水?？鄥A組造模前2dip注射用苦參堿25、50、100mg/kg,連續(xù)給藥5d。觀察大鼠心肌細胞病理學,采用酶聯(lián)免疫吸附法檢測大鼠血清線粒體偶聯(lián)因子CF6水平,應用分光光度法測定Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶活力,采用試劑盒檢測谷胱甘肽過氧化物酶(GSH-px)、總超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。結(jié)果 苦參堿各組心肌組織腫脹,肌束間、間質(zhì)有灶性出血現(xiàn)象顯著減輕。與模型組比較,苦參堿各組血清CF6水平顯著降低(P<0.05);線粒體Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶活性顯著升高(P<0.05);心肌組織GSH-px活性及SOD活力升高,MDA含量顯著降低(P<0.05)。結(jié)論 苦參堿能保護阿霉素引起的大鼠心肌損傷,其作用機制與改善線粒體ATP酶活性、降低線粒體偶聯(lián)因子6水平、減輕氧化應激水平有關(guān)。

Objective To study the protective effects of matrine against cardiac injury induced by doxorubicin in rats and explore its mechanism. Methods SD rats were randomly divided into control group, model group, and matrine (25, 50, and 100 mg/kg) groups, and each group had 20 rats. Rats in model group were ip administered with Adriamycin Injection 2.5 mg/kg, once per week, cumulative reach to 15 mg/kg, and treated for 10 d to establish cardiac injury model. Rats in control group were ip administered with equivalent normal saline. Rats in the matrine groups were ip administered with Matrine for injection 25, 50, and 100 mg/kg 2 d before models were established, and treated for 5 d. Pathological changes of cardiac muscle cells in rats were observed. The serum levels of CF6 were detected by enzyme-linked immunosorbent assay, and activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase were detected by electromicroscope. Activities of GSH-px and SOD, and contents of MDA were determined by corresponding kits. Results Myocardial tissue swelling, muscle and interstitial hemorrhage in the matrine groups were significantly reduced. Compared with the model group, serum levels of CF6 in the matrine groups were significantly decreased (P < 0.05), and activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase in mitochondrion of the matrine groups were significantly increased (P < 0.05). Compared with the model group, activities of GSH-px and SOD in myocardial tissue of the matrine groups were significantly increased, contents of MDA were significantly decreased (P< 0.05). Conclusion Matrine has protective effects against cardiac injury induced by doxorubicin in rats, whose mechanism may be related to improvement of activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase, reduction of CF6 levels, and release of oxidative stress levels.

黑龍江省自然科學基金項目(H201365);佳木斯大學科學技術(shù)重點項目(Sz2013-004)