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引用本文:刘林,李弘,任卫琼,蔺晓源,李苏,王宇红,柏正平.天麻芎苓止眩片对自发性高血压大鼠血压及血管重塑的影响[J].中国现代应用药学,2020,37(4):414-419.
LIU Lin,LI Hong,REN Weiqiong,LING Xiaoyuan,LI Su,WANG Yuhong,BAI Zhengping.Effect of Tianma Xiongling Zhixuan Tablet on Blood Pressure and Vascular Remodeling in Spontaneously Hypertensive Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(4):414-419.
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天麻芎苓止眩片对自发性高血压大鼠血压及血管重塑的影响
刘林1,2, 李弘3, 任卫琼1, 蔺晓源1, 李苏1, 王宇红3, 柏正平2
1.湖南中医药大学第一附属医院, 长沙 410007;2.湖南省中医药研究院, 长沙 410013;3.湖南中医药大学科学创新中心, 长沙 410208
摘要:
目的 探讨天麻芎苓止眩片(Tianma Xiongling Zhixuan tablet,TXZT)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)的降压作用和改善血管重塑作用。方法 采用SHR大鼠和正常WKY大鼠进行实验,连续给药4周,比较每周各组大鼠血压值;ELISA法检测血清中eNOS、ET-1、TXA2、AngⅡ的含量变化;HE染色法观察大鼠主动脉的病理变化;免疫组化和Western blotting测定主动脉MMP-2、TIMP-2蛋白表达;RT-PCR测定主动脉MMP-2、TIMP-2 mRNA表达。结果 与模型组比较,给药第1~4周,TXZT具有显著的降血压药理作用(P<0.01或P<0.05)。与模型组相比,TXZT能够有效降低SHR大鼠血清ET-1、TXA2、AngⅡ的水平,升高eNOS的水平(P<0.01或P<0.05);且能够明显改善血管病理变化。免疫组化和Western blotting结果显示,与模型组相比,TXZT能显著减弱MMP-2表达、降低MMP-2/TIMP-2比值(P<0.01或P<0.05)。RT-PCR结果显示,经TXZT治疗后大鼠血管MMP-2的mRNA表达下降,TIMP-2的mRNA表达上升,MMP-2/TIMP-2比值降低(P<0.05)。结论 TXZT具有显著的降压和改善血管内皮功能作用,调节MMP-2/TIMP-2蛋白表达是其调节SHR大鼠血管重塑作用机制之一。
关键词:  高血压  MMP-2/TIMP-2  血管内皮功能  血管重塑
DOI:10.13748/j.cnki.issn1007-7693.2020.04.006
分类号:R285.5
基金项目:国家自然科学基金项目(81473616);“重大新药创制”国家科技重大专项(2019ZX09301103);中国博士后科学基金项目(2018M632966);湖南省卫生健康委科研计划项目(C2019090);长沙市杰出创新青年培养计划项目(kq1802008);湖南省高校“双一流”建设项目(湘教通[2018]469号)
Effect of Tianma Xiongling Zhixuan Tablet on Blood Pressure and Vascular Remodeling in Spontaneously Hypertensive Rats
LIU Lin1,2, LI Hong3, REN Weiqiong1, LING Xiaoyuan1, LI Su1, WANG Yuhong3, BAI Zhengping2
1.The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China;2.Hunan Academy of Chinese Medicine, Changsha 410013, China;3.Institute of Innovation and Applied Research, Hunan University of Chinese Medicine, Changsha 410208, China
Abstract:
OBJECTIVE To explore the anti hypertensive pharmacological mechanism and vascular remodeling mechanism of Tianma Xiongling Zhixuan tablet(TXZT) in spontaneously hypertensive rats(SHR). METHODS SHR and WKY rats were used. The rats were continuously intragastrically administered for 4 weeks, observed and compared the blood pressure values of each group in each week. The levels of eNOS, ET-1, TXA2 and AngⅡ in serum were detected by ELISA. The pathological changes of rat thoracic aorta were observed by HE staining. The expression of MMP-2 and TIMP-2 in aorta was determined by immunohistochemistry, Western blotting and RT-PCR. RESULTS Compared with the model group, TXZT had a significant pharmacological effect on lowering blood pressure(P<0.01 or P<0.05). Compared with the model group, TXZT effectively reduced the levels of serum ET-1, TXA2, AngⅡ and increased the level of eNOS in SHR(P<0.01 or P<0.05), and significantly improved vascular pathological changes. Immunohistochemical and Western blotting showed that TXZT significantly reduced the expression of MMP-2 and MMP-2/TIMP-2 value compared with the model group(P<0.01 or P<0.05). RT-PCR result showed that TXZT significantly reduced the expression of MMP-2 and MMP-2/TIMP-2 value, increased the expression of TIMP-2(P<0.05). CONCLUSION TXZT has significant antihypertensive effect, improving vascular endothelial function and regulating MMP-2/TIMP-2 balance, improve vascular remodeling may be one of its important mechanisms.
Key words:  hypertension  MMP-2/TIMP-2  vascular endothelial function  vascular remodeling
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