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[摘要]
目的 探讨苦参总黄酮对异丙肾上腺素(Iso)诱导的大鼠心肌纤维化的作用及机制。方法 以Iso 5 mg/kg背部sc 7 d构建大鼠心肌纤维化模型,同时ig苦参总黄酮100、200、400 mg/kg,连续用药21 d,测定大鼠心重指数(HW/BW)和左心室重指数(LVW/BW);ELISA法测定心肌中I型、III型胶原及肿瘤坏死因子α(TNF-α)的水平;ELISA法测定血清中血管紧张素II(AngII)的水平;分光光度法检测心肌中丙二醛(MDA)水平;比色法检测心肌中NO水平,并观察心肌组织的病理改变。结果 与对照组比较,模型组大鼠HW/BW、LVW/BW和心肌中I型胶原、III型胶原、TNF-α及MDA的水平升高,血清中AngII水平增加,心肌中NO水平降低(P<0.05、0.01),HE染色可见心肌损伤及明显的纤维化病灶形成。苦参总黄酮200、400 mg/kg均能降低HW/BW、LVW/BW及心肌中I型、III型胶原、MDA水平,降低血清中AngII的水平,增加心肌中NO水平,100、200和400 mg/kg苦参总黄酮均降低心肌中TNF-α的水平,与模型组比较差异显著(P<0.05、0.01)。HE染色显示苦参总黄酮200、400 mg/kg组未见明显纤维化病灶。结论 苦参总黄酮可抑制Iso所致的大鼠心肌纤维化,其机制与提高NO水平及抗氧化作用,进而降低循环AngII的水平、抑制心肌中TNF-α及胶原的合成有关。
[Key word]
[Abstract]
Objective To explore the inhibitory effect of flavonoids from Sophora flavescens on the myocardial fibrosis induced by isoprenaline (Iso) and its mechanism in rats. Methods Myocardial fibrosis model in rats was established by sc injection with Iso (5 mg/kg) for 7 d. The model rats were treated with low-, mid-, and high-dose (100, 200, and 400 mg/kg) flavonoids from S. flavescens and captopril (50 mg/kg) respectively by ig for 21 d. Myocardial indexes (heart weight/body weight, HW/BW and left ventricular weight/body weight, LVW/BW) were measured after the experiment was finished. The contents of collagen I, collagen III, tumor necrosis factor α (TNF-α) in myocardium and the level of angiotensin II (AngII) in blood serum were determined by ELISA. The concentration of malondialdehyde (MDA) in myocardium was assayed with spectrophotometry. The content of nitric oxide (NO) in myocardium was detected with colorimetry. The pathological changes of myocardium were observed. Results Compared with the control group, the myocardial indexes and the contents of collagen I, collagen III, TNF-α, MDA in myocardium, and the level of AngII in blood serum were markedly increased, the content of NO in myocardium was decreased in the model group (P < 0.05, 0.01). Compared with the model group, the myocardial indexes, the contents of collagen I, collagen III, MDA in myocardium, and the level of AngII in blood serum were markedly reduced, the content of NO in myocardium was increased in mid-and high-dose flavonoids from S. flavescens groups (P < 0.05, 0.01). The level of TNF-α in myocardium was reduced in all flavonoids from S. flavescens groups (P < 0.05, 0.01). HE staining showed that myocardial tissue had obviously myocardial damage and the formation of fibrosis lesions in the model group; The myocardial tissue had few fibrosis lesions in mid-and high-dose flavonoids from S. flavescens groups. Conclusion Flavonoids from S. flavescens could inhibit myocardial fibrosis and protect myocardium in rats, and its mechanism may be associated with decreasing AngII level in circulation and myocardium, lowering TNF-α content in myocardium, and inhibiting collagen synthesis by increasing the NO level and anti-oxidation.
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[基金项目]
吉林省教育厅“十二五”科技研究项目资助课题(2012337)