原花青素对D-半乳糖复合三氯化铝诱导大鼠主动脉损伤的保护作用及机制

Mechanisms and protective effect of procyanidins on the aortal injury in rats induced by D-galactose combined with aluminum trichloride

目的:探讨原花青素对D-半乳糖(D-gal)复合三氯化铝(AlCl3)诱导大鼠主动脉损伤的保护作用及可能机制。方法:采用D-半乳糖腹腔注射(i.p.)180mg·kg-1·d-1联合三氯化铝灌胃(i.g.)15mg·kg-1·d-1建立主动脉损伤大鼠模型,12周后将40只大鼠随机分为空白对照组(NS i.p.,NS i.g.),主动脉损伤组(D-gal i.p.+AlCl3i.g.),原花青素低、高剂量组(PC 20、40mg/kg;D-gal i.p.+AlCl3i.g.),维生素E组(VitE 10mg/kg;D-gal i.p.+AlCl3i.g.),每组8只。每日灌胃给药一次,连续8周。于末次给药后,尾袖法测量大鼠尾动脉血压;离体灌流法观察主动脉环对乙酰胆碱的舒张反应;HE染色观察主动脉病理变化;化学比色法测定血清总抗氧化能力(T-AOC)、过氧化氢(H2O2)以及NO含量;免疫组化法观察主动脉内皮型一氧化氮合酶(eNOS)表达。结果:与模型组相比,随着原花青素剂量的增加,大鼠血压逐渐降低,主动脉内皮依赖性舒张功能逐渐增强,主动脉病理损伤得到不同程度的改善;血清中总抗氧化能力和NO含量逐渐增高,H2O2含量逐渐降低;主动脉eNOS蛋白表达逐渐增加。结论:原花青素可明显降低主动脉血压,增强主动脉环内皮依赖性舒张反应,减轻主动脉病理损伤,增高血清NO水平,上调主动脉eNOS蛋白的表达,对D-半乳糖复合三氯化铝诱导的大鼠主动脉损伤有一定保护作用。

AIM： To observe the protective effect of procyanidins on the aortal injury in rats induced by D-galactose combined with aluminum trichloride and explore its conceivable mechanisms. METHODS： The model of aortal injury rats were established by intraperitoneal injection of D-galactose（180mg/kg/d）combined with intragastric of aluminum chloride（15mg/kg/d）. 12 weeks later, aortal injury rats（40） were randomized into blank control group （NS ip, NS ig）, aortal injury group （D-gal ip ＋ AlCl3 ig）, procyanidins with low and high dosages （PC 20,40 mg / kg ; D-gal ip ＋ AlCl3 ig）, vitamin E group （VitE 10 mg / kg; D-gal ip ＋ AlCl3 ig） （ n= 8 for each group）. The animals were intragastrically administrated with procyanidins once a day for consecutive 8 weeks．After the last administration, blood pressure was measured by tail cuff；The thoracic aortic ring of rats was mounted on a bath system,and the relaxation induced by acetylcholine was measured; The primary pathologic changes of aorta were observed by HE staining;T-AOC ,H2O2and NO in serum were measured by colorimetric analysis；The expression of eNOS protein were measured by immunohistochemistry. RESULTS： With the increase dose of procyanidins, the blood pressure was gradually decreased ,the aortic endothelium-derived diastolic function had been improved,the aortal pathological damage had been improved; The levels of serum T-AOC and NO were gradually increased while the level of serum H2O2 was gradually decreased. The expression of eNOS protein upregulated inch by inch. CONCLUSION： Procyanidins can significantly decrease the blood preasure,improve the aortic endothelium-derived diastolic function, ameliorate the aortal injury,suggesting this medicine may protect the aorta from injury through increasing the level of serum NO and the expression of eNOS protein expression.