| 引用本文:张颖1，周明学2，李思耐2，任攀2，刘卫红2，尚菊菊2，刘红旭3.丹红注射液对动脉粥样硬化小鼠主动脉斑块的干预作用及基因组DNA甲基化水平和甲基化转移酶的影响[J].世界中医药,2017,(02):. |
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| 丹红注射液对动脉粥样硬化小鼠主动脉斑块的干预作用及基因组DNA甲基化水平和甲基化转移酶的影响 |
| Effects of Danhong Injection on Atherosclerotic Plaque and Global Genomic DNA Methylation and the DNMTs in Atherosclerotic Mice |
| 投稿时间：2017-02-10 |
| DOI：10.3969/j.issn.1673-7202.2017.02.003 |
| 中文关键词: 动脉粥样硬化 丹红注射液 DNA甲基化；血脂异常 DNA甲基化转移酶1 |
| English Keywords:Atherosclerosis Danhong injection Dyslipidemia DNA methyltransferase 1 Peroxisome proliferator activated receptor gamma |
| 基金项目:国家自然科学基金项目(编号：81673744)；北京市自然科学基金项目（编号：7162043）；北京市卫生系统高层次卫生技术人才项目(编号：2014-3-100) |
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| 中文摘要: |
| 目的：研究丹红注射液对高脂喂养的ApoE基因敲除(ApoE-/-)小鼠动脉粥样硬化(As)斑块的干预作用及基因组DNA甲基化水平和DNA甲基化转移酶(DNMTs)的影响。方法：将40只8周龄雄性ApoE-/-小鼠高脂饲料喂养6周后随机分为模型组、阿托伐他汀钙片（商品名：立普妥）(阳性对照组)、丹红注射液低剂量组和高剂量组(n=10)，给予药物腹腔注射6周后。检测其血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。行HE染色，图像分析测量小鼠主动脉As斑块面积。采用高效液相色谱（HPLC）法检测小鼠血清基因组甲基化水平，采用ELISA法检测各组小鼠血清DNMTs水平。免疫组化染色，图像分析测量小鼠主动脉As斑块内DNMT1的表达。结果：与模型组相比，丹红注射液高剂量和低剂量组小鼠血清TG水平明显降低（P<0.01)、丹红注射液高剂量组LDL-C水平明显降低（P<0.01)，丹红注射液低剂量组HDL-C水平明显升高（P<0.05)，丹红注射液高剂量组小鼠动脉粥样硬化指数显著降低（P<0.01)。丹红注射液高剂量和低剂量组小鼠血清基因组甲基化和DNMTs水平显著降低（P<0.01)。丹红注射液与模型组相比，丹红注射液组As小鼠的校正后主动脉As斑块面积显著降低，以及斑块内DNMT1表达显著降低（P<0.01)。结论：丹红注射液可降低As小鼠血脂水平，减少As斑块面积，其机制可能与降低As小鼠血清基因组甲基化水平和整体DNMTs水平和抑制As小鼠主动脉斑块DNMT1表达有关。 |
| English Summary: |
| To study the effects of Danhong Injection on atherosclerotic plaque and the levels of the global genomic DNA methylation and DNMTs in ApoE knockout (ApoE-/-) mice fed with a high fat diet.Methods:Forty 8 week-old male ApoE-/-mice were fed with a high fat diet for 6 weeks were randomly divided into the control group,the Lipitor (positive control group),the Danhong injection low-dose group (DHI-L group),and the Danhong injection high-dose group (DHI-H group),then were intraperitoneally injected corresponding medicine for 6 weeks,n=10.The levels of total cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C) in serum were detected.HE staining was used to measure the area of As plaque of mice.Immuno-histochemical staining and image analysis were used to measure the expressions of DNMT1 in the Atherosclerosis (As) plaques of mice.Results:Compared with the control group,the TG levels in serum of the mice in the DHI-L group and DHI-H group were significantly decreased (P<0.01),and the LDL-C levels on DHI-H group were significantly decreased (P<0.01).Besides,the HDL-C levels in DHI-L group were significantly increased (P<0.05).The atherosclerosis indexes of the mice in DHI-H group were significantly decreased (P<0.01).The levels of global genomic DNA methylation and the DNMTs in serum of the mice on the DHI-L group and DHI-H group were significantly decreased (P<0.01).Compared with the control group,the atherosclerotic plaque areas of the mice on the DHI-L group and DHI-H group were significantly reduced (P<0.01),and the expressions of DNMT1 on the DHI-L group and DHI-H group were significantly reduced (P<0.01).Conclusion:Danhong Injection can reduce the blood lipid level and the plaque area of As mice.The mechanism can be related to the reduction of levels of global genomic DNA methylation and the DNMTs in serum and the inhibition of DNMT1 expression in the aortic plaques of As mice. |
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