苦参总黄酮对异丙肾上腺素所致大鼠心肌纤维化的影响

Effect of flavonoids from Sophora flavescens on the myocardial fibrosis induced by isoprenaline in rats

目的:探讨苦参总黄酮(flavonoids from Sophora flavescens)对大鼠心肌纤维化的作用及其机制。方法:以异丙肾上腺素(isoprenaline,Iso)5 mg/kg背部皮下注射7d构建大鼠心肌纤维化模型,同时以灌胃方式给予苦参总黄酮100、200、400 mg/kg,连续用药21d,实验结束后测量大鼠心脏重量指数(HW/BW)和左心室重量指数(LVW/BW);ELISA法测定心肌中血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)的含量;分光光度法检测左心室心肌组织中羟脯氨酸(hydroxyproline,Hyp)含量及超氧化物歧化酶(superoxide dismutase,SOD)活性、血清中丙二醛(malondialdehyde,MDA)及肌酸磷酸激酶(creatine kinase,CK)含量;比色法检测血清中一氧化氮(nitric oxide,NO)含量的变化。结果:与对照组比较,Iso模型组大鼠心重指数和左心室重量指数增高,心肌中AngⅡ的含量增加、Hyp含量增高、SOD活性降低,血清中NO含量降低、MDA含量及CK活性增加。苦参总黄酮200、400mg/kg均能降低心重指数和左心室重量指数、增加SOD的活性、降低血清中CK的含量,苦参总黄酮100、200和400mg/kg降低心肌中AngⅡ的含量、减少心肌组织中的Hyp含量、增加血清中NO含量、降低血清中MDA的含量,同模型组比较有统计学差异。结论:苦参总黄酮可抑制异丙肾上腺素所致的大鼠心肌纤维化,机制与降低心肌局部AngⅡ的水平、抗氧化作用及提高NO水平而抑制胶原的合成有关。

Obejective： To explore the effect of flavonoids from Sophora flavescens on the myocardial fibrosis and its mechanism in rats.Methods： Isoprenaline（5 mg / kg） was injected subcutaneously for 7 days to induce myocardial fibrosis.Flavonoids from Sophora flavescens（100,200 and 400mg / kg） groups were treated by gastrointestinal administration for 21 days.Myocardial indexes（heart weight / body weight,HW / BW and left ventricular weight / body weight,LVW / BW） were measured after the experiment was finished.Angiotensin Ⅱ level in left ventricle was determined by the ELISA.The content of nitric oxide（NO） in blood serum was determined with colorimetry.Hydroxyproline（Hyp） and superoxide dismutase（SOD） levels in left ventricle,malondialdehyde（MDA） concentration and creatine kinase（CK） activity in blood serum were also estimated respectively with spectrophotometry.Results： Compared with the control group,the myocardial indexes,the levels of angiotensin Ⅱ,Hyp in left ventricle and MDA in blood serum were markedly increased,the level of SOD in left ventricle and the content of NO in blood serum were decreased,the activity of CK in blood serum were markedly enhanced in Iso model group（P ＆lt; 0.05 or P ＆lt; 0.01）.Compared with model group,the myocardial indexes were reduced,the activity of CK in blood serum were markedly lessened,the activity of SOD in left ventricle were increased in flavonoids from sophora flavescens 200 and 400mg / kg groups（P ＆lt; 0.05 or P ＆lt; 0.01）.The levels of Hyp,angiotensin Ⅱ in left ventricle were reduced,the content of NO in blood serum was increased,the content of MDA in blood serum was markedly decreased in flavonoids from Sophora flavescens three groups（P ＆lt; 0.05 or P ＆lt; 0.01）.Conclusion： Flavonoids from Sophora flavescens could inhibit myocardial fibrosis and protect myocardium in rats,its mechanism may be associated with inhibiting collagen synthesis by decreasing angiotensin Ⅱlevel,increasing the content of NO and antioxidation.