柿根水提液对L-NAME诱导的高血压大鼠的降压作用研究

Effect of water extract of persimmon root on L-NAME induced hypertension in rats

目的:研究柿根水提液(PRE)对一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯(L-NAME)诱导的高血压大鼠的降血压作用及其机制。方法:将48只Wistar大鼠随机分为6组,即空白对照组、模型组、卡托普利组(10mg/kg·d^-1)、PRE高剂量(PREH)组(10g/kg·d^-1)、PRE中剂量(PREM)组(5g/kg·d^-1)和PRE低剂量(PREL)组(2.5g/kg·d^-1),每组8只。采用L-NAME灌胃给药复制高血压大鼠模型,造模成功后,给予PRE干预,每周测大鼠尾动脉压,干预4周后处死大鼠,用比色分析法测定大鼠血清中丙二醛(MDA)和一氧化氮(NO)的含量、总超氧化物歧化酶活性(T-SOD)和总抗氧化能力(T-AOC);采用酶联免疫吸附试验(ELISA)法测定大鼠心肌组织中肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的含量;苏木精—伊红(HE)染色法观察心肌和肾脏组织病理学改变。结果:与模型组相比较,PRE各剂量组均能使L-NAME诱导的高血压大鼠血压明显降低,以高剂量组最为显著(P<0.05);血清MDA含量显著降低,NO、T-SOD、T-AOC含量显著升高(P<0.05或P<0.01);PRE各剂量组大鼠心肌组织TNF-α和TGF-β1含量均降低(均P<0.01)。PRE各剂量组心肌组织病理改变明显减轻。结论:PRE可降低L-NAME诱导的高血压大鼠的血压,其机制可能是通过增加NO的生成和释放,抗自由基,抑制脂质过氧化损伤,降低心肌TNF-α及TGF-β1因子的表达水平,从而发挥其降压作用。

Objective: To explore the effect and mechanism of water extract of persimmon root(PRE) on L-NAME induced hypertensive in rats. Methods: Fourty-eight rats were randomly divided into six groups( n =8 each),which were given by gavage once a day for 4 weeks:a normal control group (normal saline),a model group (treated with L-NAME alone),captopril group(treated with captopril at dose of 10 mg/kg),and three different doses of PRE groups (10g/kg,5g/kg,2.5g/kg).PRE was orally administered for 4 weeks after the hypertension was established by L-NAME treatment in rats,which tail blood pressure was measured every week.Rats were sacrificed to determine blood serum malondialdehyde (MDA),nitric oxide (NO),total superoxide dismutase(T-SOD) activity and total antioxidant capacity(T-AOC),the levels of tumor necrosis factor α(TNF-α) and transforming growth factor β 1 (TGF-β 1 ) in myocardial tissue after 4 weeks of treatment.HE staining was performed to observe the pathological changes. Results: PRE could decrease the tail blood pressure of rats,and the hypotensive effect was the most significant in the PRE H group( P <0.05).The content of NO,the activities of T-SOD and T-AOC were increased significantly ( P <0.05 or P <0.01) in each treatment group,meanwhile the content of MDA in the plasma was decreased significantly ( P <0.05 or P <0.01) as compared with the model group.Compared with the model group,the expression of TNF-α,TGF-β 1 in the rats’ myocardium in each treatment group decreased significantly( P <0.01).The myocardial tissue histopathalogical of PRE groups were obviously improved. Conclusion: PRE can reduce blood pressure in L-NAME induced hypertension rats,it shows that PRE may play a role in reducing blood pressure through the increase of NO releasing,the antagonism of free-radical,and the inhibition of lipid peroxidation,is also due to decreasing the expression of TNF-α and TGF-β1 in myocardium.