目的:研究参麦注射液干预高血压心衰的生物学机制。方法:通过高盐饲料(含8%Nacl)喂养Dahl盐敏感大鼠20周建立高血压心衰大鼠模型,另以普通饲料(含0.3%Nacl)喂养建立正常大鼠(8只),成模大鼠分为模型组(8只)和参麦注射液组各8只。药物干预...目的:研究参麦注射液干预高血压心衰的生物学机制。方法:通过高盐饲料(含8%Nacl)喂养Dahl盐敏感大鼠20周建立高血压心衰大鼠模型,另以普通饲料(含0.3%Nacl)喂养建立正常大鼠(8只),成模大鼠分为模型组(8只)和参麦注射液组各8只。药物干预15 d后采集所有大鼠的血清样本,运用液相色谱-质谱(liquid chromatography mass spectrometry,LC-MS)联用的代谢组学技术筛选组间差异代谢产物,分析关联代谢通路。结果:3组大鼠的代谢轮廓具有差异,与模型组比较参麦注射液组的四氢嘧啶、谷氨酸、腺嘌呤、异柠檬酸、乙酰乙酸、尸胺、12,13-二氢乳清酸表达水平向正常方向显著回调,涉及丁酸代谢通路、酮体的合成与降解通路、D-谷氨酰胺和D-谷氨酸代谢通路、谷胱甘肽代谢通路等4条代谢路径。结论:参麦注射液可促使氨基酸、酮体等代谢产物水平趋于正常化,调控能量代谢相关路径,从而优化心脏能量供应。展开更多
Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the ...Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.展开更多
文摘目的:研究参麦注射液干预高血压心衰的生物学机制。方法:通过高盐饲料(含8%Nacl)喂养Dahl盐敏感大鼠20周建立高血压心衰大鼠模型,另以普通饲料(含0.3%Nacl)喂养建立正常大鼠(8只),成模大鼠分为模型组(8只)和参麦注射液组各8只。药物干预15 d后采集所有大鼠的血清样本,运用液相色谱-质谱(liquid chromatography mass spectrometry,LC-MS)联用的代谢组学技术筛选组间差异代谢产物,分析关联代谢通路。结果:3组大鼠的代谢轮廓具有差异,与模型组比较参麦注射液组的四氢嘧啶、谷氨酸、腺嘌呤、异柠檬酸、乙酰乙酸、尸胺、12,13-二氢乳清酸表达水平向正常方向显著回调,涉及丁酸代谢通路、酮体的合成与降解通路、D-谷氨酰胺和D-谷氨酸代谢通路、谷胱甘肽代谢通路等4条代谢路径。结论:参麦注射液可促使氨基酸、酮体等代谢产物水平趋于正常化,调控能量代谢相关路径,从而优化心脏能量供应。
基金Supported by Hunan Provincial Natural Science Foundation of China(No.2020JJ5408)Scientific Research Fund of Hunan Provincial Education Department(No.21B0361)+1 种基金Research Fund of Hunan University of Chinese Medicine(No.2019XJJJ012)Zhuzhou Second Batch of Science and Technology Guidance Projects(No.2017-17)。
文摘Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.
