摘要
目的:探讨四妙勇安汤活性部位对一氧化氮合成酶抑制剂(L-NAME)诱导的高血压大鼠血管重构的作用及其机制。方法:48只Wistar大鼠随机分为6组,分别为四妙勇安汤活性部位高、中、低剂量组(1,0.5,0.25 g·kg-1·d-1),卡托普利组(50 mg·kg-1·d-1),辛伐他汀阳性药物组(10 mg·kg-1·d-1)及模型组,各组动物饮水中给予L-NAME(1 g·L-1)。给药第4周后,测定动物体重、心脏质量、血压、心率;处死后,主动脉根部切片苏木素-伊红(HE)染色,测定主动脉厚度变化;马松(Masson)染色观察冠状动脉纤维化变化;免疫组化方法观察单核巨噬细胞抗原-1(ED-1)和增殖细胞核抗原(PCNA)的表达变化。结果:与模型组比较,仅卡托普利组具有减轻心肌肥厚的作用;卡托普利组、四妙勇安汤活性部位高、中剂量组具有一定降低舒张压和收缩压的作用;与模型组比较,给药各组对心率均没有影响;卡托普利组、四妙勇安汤活性部位高、中剂量组可明显降低主动脉壁厚;卡托普利组、四妙勇安汤活性部位高剂量组可降低可明显减少冠状动脉周边纤维化的形成;卡托普利组、四妙勇安汤活性部位高剂量组可明显抑制冠状动脉ED-1和PCNA的表达(P<0.05,P<0.01)。结论:四妙勇安汤活性部位具有降低高血压作用,改善血管重构,其机制可能与其抑制冠状动脉ED-1的抗炎作用和抑制PCNA的抗增殖作用相关。
Objective: To explore the effect and mechanism of the active fraction of Simiao Yongan Tang( AFSM) on vascular remodeling in hypertensive rats induced by nitric oxide synthase inhibitor( L-NAME).Method: Forty-eight Wistar rats were randomly divided into six groups: AFSM high dose group,medium dose group and low dose group( 1,0. 5,0. 25 g·kg- 1·d- 1),captopril group( 50 mg·kg- 1·d- 1),simvastatin positive drug group( 10 mg·kg- 1·d- 1) and model group. L-NAME was administered to the animals in each group. Their body weight,heart weight,blood pressure and heart rate were determined after four weeks of administration. After sacrificing,their aortic thickness changes were measured through HE staining on aortic root slice. Masson staining was used to observe the changes of the coronary artery fibrosis,and the changes of the expression levels of monocyte macrophage antigen-1( ED-1) and proliferating cell nuclear antigen( PCNA) were observed by immunohistochemistry method. Result: As compared with the model group,only captopril group could alleviate myocardial hypertrophy; captopril group,AFSM high dose and medium dose groups had certain effects in reducing diastolic and systolic blood pressure; there was no effect on heart rate in various treatment groups; captopril group,AFSM high dose and medium dose groups could significantly reduce the aortic wall thickness; captopril group and AFSM high dose group could significantly reduce the formation of peripheral fibrosis of the coronary artery;captopril group and AFSM high dose group could significantly inhibit the expression levels of ED-1 and PCNA in the coronary artery( P < 0. 05,P < 0. 01). Conclusion: The AFSM active fractions can reduce hypertension and improve vascular remodeling. The mechanism may be related to inhibiting the anti-inflammatory effect of ED-1 and the anti-proliferative effect of PCNA.
引文
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