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当归挥发油对自发性高血压大鼠miR-155及其靶基因的影响     被引量:6

Effect of Angelica Naphtha on the Expression Levels of miR-155 and Target Genes in Spontaneously Hypertensive Rats

文献类型:期刊文献

中文题名:当归挥发油对自发性高血压大鼠miR-155及其靶基因的影响

英文题名:Effect of Angelica Naphtha on the Expression Levels of miR-155 and Target Genes in Spontaneously Hypertensive Rats

作者:纪禄风[1,2];石向慧[1];王立红[1];伊琳[1]

第一作者:纪禄风

机构:[1]甘肃中医药大学中西医结合学院,甘肃省兰州市730000;[2]甘肃中医药大学中西医结合重点实验室,甘肃省兰州市730000

第一机构:甘肃中医药大学中西医结合学院

年份:2017

卷号:20

期号:9

起止页码:1055

中文期刊名:中国全科医学

外文期刊名:Chinese General Practice

收录:CSTPCD;;Scopus;北大核心:【北大核心2014】;

基金:国家自然科学基金资助项目(81460669)--基于miRNA与RAS系统探讨当归降压的分子机制研究;甘肃省自然科学基金资助项目(1310RJZA084)--当归提取液对自发性高血压大鼠miRNA差异表达谱的影响

语种:中文

中文关键词:高血压;当归挥发油;miR-155;血管紧张素Ⅱ1型受体拮抗剂

外文关键词:Hypertension; Angelica naphtha; miR-155; Angiotensin Ⅱ type 1 receptor blockers

摘要:目的探究当归挥发油对自发性高血压大鼠(SHR)miR-155及其靶基因的影响,并从肾素-血管紧张素-醛固酮系统(RAAS)探讨当归挥发油对SHR血压的改善作用及其机制。方法 2015年10月—2016年4月,将8周龄48只SPF级雄性SHR随机分为模型组、当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组,各8只;另选取8只SPF级正常血压雄性Wistar大鼠作为正常组。正常组、模型组不给予任何药物,当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠分别灌胃给予当归挥发油乳剂12.6 mg·kg^(-1)·d^(-1)、37.0 mg·kg^(-1)·d^(-1)、100.0 mg·kg^(-1)·d^(-1),藁本内酯溶液0.8 mg·kg^(-1)·d^(-1),缬沙坦溶液51.4 mg·kg^(-1)·d^(-1),连续给药4周,给药期间各组大鼠标准饮食、自由饮水。检测给药前及给药第1、2、3、4周各组大鼠收缩压变化。灌胃4周后处死大鼠取心脏,HE染色观察心肌组织病理学的变化,采用Western blotting法检测血管紧张素Ⅱ1型受体(AT1R)、细胞外调节蛋白激酶1/2(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)表达水平。采用RT-qPCR法检测miR-155表达水平。结果不同处理情况、时间在大鼠收缩压中存在交互作用(P<0.05);不同处理情况、时间在大鼠收缩压中主效应显著(P<0.05)。给药前及给药第1、2、3周,模型组、当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠收缩压均高于正常组(P<0.05);给药第4周模型组大鼠收缩压高于正常组(P<0.05);给药前当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠收缩压均高于模型组,给药第1、2、3、4周当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠收缩压均低于模型组(P<0.05)。HE染色显示,模型组大鼠心肌组织红细胞多而挤,心肌横纹不清,提示心肌充血,右心功能受损;当归挥发油低、中、高剂量组大鼠心肌组织出现横纹且清晰。当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠AT1R、ERK1/2、p-ERK1/2表达水平均低于模型组(P<0.05)。7组大鼠miR-155表达水平比较,差异无统计学意义(P>0.05)。结论当归挥发油能够明显抑制AT1R基因的表达,通过调节ERK1/2信号通路从而达到降压的功能;当归挥发油不通过miR-155在心肌组织发挥作用。
Objective To study the effect of angelica naphtha on the expression levels of miR-155 and target genes inspontaneously hypertensive rats( SHR), and to investigate the influence and mechanism of action of angelica naphtha on lowering the blood pressure in SHR from the perspective of renin angiotensin aldosterone system( RAAS). Methods This study was conducted between October 2015 and April 2016. We randomized 48 SPF male SHR rats aged 8 weeks old into model group,low-dose angelica naphtha group,medium-dose angelica naphtha group, high-dose angelica naphtha group, ligustilide group,valsartan group with 8 SHR rats in each group,and selected 8 SPF male Wistar rats with normal blood pressure as the normal group. Low-dose angelica naphtha group,medium-dose angelica naphtha group,high-dose angelica naphtha group,ligustilide group,valsartan group were given intragastric administration of angelica naphtha emulsion 12.6mg·kg-(-1)·d-(-1),37.0mg·kg-(-1)·d-(-1),100.0mg·kg-(-1)·d-(-1), ligustilide solution 0.8mg·kg-(-1)·d-(-1), valsartan solution 51.4mg·kg-(-1)·d-(-1),respectively,once a day,for 4 weeks,while both the normal group and model group were not given any drugs during this period. All the groups had standard diet,and they could drink water freely during this period of intervention. Systolic blood pressure( SBP) was measured in each group before the intervention, at the 1st, 2nd, 3rd, and 4th weeks of intervention. All the rats were sacrificed and the heart was taken at the end of intervention. HE staining was used to recognize the morphologic changes in cardiac tissue. Western blotting was employed to determine the expression levels of angiotensin Ⅱ type 1receptor( AT1R),extracellular signal-regulated kinase 1/2( ERK1/2) and phosphorylated ERK 1/2( p-ERK1/2). And RT-qPCR was adopted to measure the expression level of miR-155. Results There was interaction on SBP in rats among different treatment ways and time( P〈0.05). There was significant effect on SBP in rats among different treatment ways and time( P〈0.05). Before the intervention,and at the 1st,2nd,3rd weeks of intervention,the SBP was lower in the normal group than in other groups( P〈0.05). The 4th week of intervention,the SBP in model group was higher than nomal group( P〈0.05). The SBP was lower in the model group than in other groups except the normal group before the intervention( P〈0.05),while it was higher in the model group than in other groups except the normal group at the 1st,2nd,3rd,4th weeks of intervention( P〈0.05). HE staining showed that,the model group had unclear myocardial stripes with erythrocytes crowded in the cardiac tissue,which suggested that myocardial hyperemia and right ventricular dysfunction occurred in the group; low-dose,medium-dose, and high-dose angelica naphtha groups had clear myocardial stripes. The model group had higher expression levels of AT1R,ERK1/2,and p-ERK1/2 than low-dose,medium-dose,and high-dose angelica naphtha groups,ligustilide group,and valsartan group( P〈0.05). The expression level of miR-155 did not differ significantly between all the groups( P〉0.05). Conclusion Angelica naphtha could significantly inhibit the expression of AT1R gene; by adjusting the ERK1/2 signaling pathway, it could lower the blood pressure; it did not affect the cardiac function via the expression of miR-155.

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