三七总皂苷对慢性心力衰竭大鼠心功能的改善作用及其机制

目的：观察三七总皂苷对慢性心力衰竭（CHF）模型大鼠心功能的改善作用，探讨其可能机制。方法：采用腹主动脉缩窄术建立CHF大鼠模型。将60只模型大鼠随机分为模型组，阳性对照组，低、中和高剂量三七总皂苷组，每组12只；另取12只大鼠作为假手术组。彩色多普勒超声检测大鼠左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）、左室后壁舒张期厚度（LVPWD）、左室射血分数（LVEF）、心输出量（CO）、左室舒张末压（LVEDP）、左室收缩压（LVSP）、左心室压力最大上升速率（+dp/dt max）和左心室压力最大下降速率（-dp/dt max），HE染色观察各组大鼠心肌组织病理形态表现，TUNEL法检测各组大鼠心肌细胞凋亡率，Western blotting法检测各组大鼠心肌组织中细胞外信号调节激酶（ERK）、磷酸化ERK （p-ERK）、c-Jun氨基末端激酶（JNK）、磷酸化JNK （p-JNK）、p38和p-p38蛋白表达水平，ELISA法检测各组大鼠血清肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）水平。结果：与假手术组比较，模型组大鼠LVEDD、LVESD、LVPWD、LVEDP和-dp/dt max明显升高（P<0.05），LVEF、CO、LVSP及+dp/dt max明显降低（P<0.05）；与模型组比较，阳性对照组和低、中及高剂量三七总皂苷组大鼠LVEDD、LVESD、LVPWD、LVEDP和-dp/dt max明显降低（P<0.05），LVEF、CO、LVSP和+dp/dt max明显升高（P<0.05）。模型组大鼠心肌细胞肥大、坏死，心肌纤维排列不规则，出现炎性细胞浸润，大量心肌细胞凋亡，阳性对照组和低、中及高剂量三七总皂苷组大鼠心肌组织结构较完整，心肌细胞肥大减轻，心肌纤维排列疏松。与假手术组比较，模型组大鼠心肌细胞凋亡率明显升高（P<0.05），心肌组织中p-ERK、p-JNK和p-p38蛋白表达水平明显升高（P<0.05），血清TNF-α和IL-6水平明显升高（P<0.05）。与模型组比较，阳性对照组和低、中及高剂量三七总皂苷组大鼠心肌细胞凋亡率明显降低（P<0.05），心肌组织中p-ERK、p-JNK和p-p38蛋白表达水平明显降低（P<0.05），血清TNF-α和IL-6水平明显降低（P<0.05）。结论：三七总皂苷可通过下调心肌组织中p-ERK、p-JNK和p-p38蛋白表达水平，抑制血清炎性因子分泌，从而抑制心肌细胞调亡，对CHF有一定的改善作用。

Improvement effect of panax notoginseng saponins on cardiac function in rats with chronic heart failure and its mechanism

Objective: To observe the improvement effect of panax notoginseng saponins on the cardiac function of the rats with chronic heart failure(CHF), and to investigate the possible mechanism. Methods: Abdominal aortic constriction was used to establish the CHF rat models. Sixty model rats were randomly divided into model group, positive control group, low, medium and high doses of panax notoginseng saponins groups (n=12).Another 12 rats were taken as sham operation group. Color doppler ultrasound was used to detect the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall diastolic thickness (LVPWD), left ventricular ejection fraction (LVEF), cardiac output (CO), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of increase of left ventricular pressure(+dp/dt max) and maximal rate of decrease of left ventricular pressure(-dp/dt max) of the rats in various groups,HE staining was used to observe the pathomorphology of myocardium tissue of the rats in various groups,TUNEL method was used to detect the apoptotic rates of cadiomyocytes of the rats in various groups,and Western blotting method was used to detect the expression levels of extracellular signal-regulated kinase(ERK),phosphorylation ERK (p-ERK),c-Jun NH2-terminal protein kinase(JNK),phosphorylation JNK(p-JNK),p38, and p-p38 proteins in myocardium tissue of the rats in various groups. ELISA was used to determine the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) of the rats in various groups. Results: Compared with sham operation group, the LVEDD, LVESD, LVPWD, LVEDP and -dp/dt max of the rats in model group were significantly increased(P<0.05), while the LVEF, CO, LVSP, and +dp/dt max were significantly decreased(P<0.05). Compared with model group, the LVEDD, LVESD, LVPWD, LVEDP and -dp/dt max of the rats in positive control group and low, medium and high doses of panax notoginseng saponins groups were significantly decreased(P<0.05), while the LVEF, CO, LVSP and +dp/dt max were significantly increased (P<0.05).The cardiomyocytes of the rats in model group were hypertrophy and necrosis, and the myocardial fibers were irregular arrangement, with inflammatory cell infiltration and myocardial cell apoptosis. The structure of myocardium tissue of the rats in positive control group and low, medium and high doses of panax notoginseng saponins groups were nearly complete, the cardiomyocyte hypertrophy was relieved, and the myocardial fibers were slagking. Compared with sham operation group, the apoptotic rate of cardiomyocytes of the rats in model group was significantly decreased(P<0.05), the expression levels of p-ERK,p-JNK,and p-p38 proteins in myocardium tissue of the rats in model group were significantly increased(P<0.05), the serum levels of TNF-α and IL-6 of the rats in model group were significantly increased (P<0.05).Compared with model group, the apoptotic rates of cardiomyocytes of the rats in positive control group and low, medium and high doses of panax notoginseng saponins groups were significantly decreased(P<0.05), the expression levels of p-ERK,p-JNK,p-p38 proteins in myocardial tissue were significantly decreased (P<0.05), and the serum levels of TNF-α and IL-6 were significantly decreased(P<0.05). Conclusion: Panax notoginseng saponins can inhibit the apoptosis of the cardiomyocytes and improve the CHF by down-regulating the expression levels of p-ERK,p-JNK and p-p38 proteins and inhibiting the secretion of serum inflammatory factors.