Huang Guangyao, Cheng Pan, Ding Ling, Wang Li, Hu Juan, Zhang Yongxue, Cai Guowei, Chen Meiling, Shen Aizong, Gao Shan
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Department of Pharmacy, Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, P.R. China.
Exp Ther Med. 2019 Mar;17(3):1551-1562. doi: 10.3892/etm.2018.7105. Epub 2018 Dec 17.
The aim of the present study was to investigate the effects of Xin-Ji-Er-Kang (XJEK) on high salt-induced hypertensive mice. Mice with high-salt diet-induced hypertension were divided into four groups: Control (standard diet alone for 8 weeks), model (diet containing 8% NaCl for 8 weeks and intragastric administration of distilled water for the last 4 weeks), XJEK + high-salt-treated (diet containing 8% NaCl for 8 weeks and intragastric administration of XJEK for the last 4 weeks) and irbesartan + high-salt-treated (diet containing 8% NaCl for 8 weeks with intragastric administration of irbesartan for the last 4 weeks). The hemodynamic index and cardiac pathological changes in the hypertensive mice were then examined. An aortic ring apparatus was used to detect acetylcholine-dependent endothelium relaxation function. Colorimetric analysis was applied to determine serum nitric oxide (NO), superoxide dismutase activity and malondialdehyde content; ELISA was employed to measure brain natriuretic peptide, serum angiotensin II (Ang II), endothelin-1 content and aldosterone; and immunohistochemistry was used to detect the expression of endothelial nitric oxide synthase (eNOS), interleukin (IL)-1β, IL-10 and tumor necrosis factor (TNF)-α in cardiac tissues. XJEK improved the heart systolic and diastolic function, ameliorated hemodynamic parameters and cardiovascular remodeling indices, blunted the cardiac pathological changes and improved endothelial dysfunction (ED) via boosting eNOS activity, promoting NO bioavailability and decreasing serum Ang II content. Furthermore, treatment with XJEK inhibited the increase of IL-1β and TNF-α expression and the decrease of IL-10 expression in cardiac tissues, and ameliorated oxidative stress status. Therefore, XJEK exerted protective effects against high salt-induced hypertension and cardiovascular remodeling in mice via improving ED, restoring pro- and anti-inflammatory factor balance and decreasing oxidative stress.
本研究旨在探讨辛芪二康(XJEK)对高盐诱导的高血压小鼠的影响。将高盐饮食诱导的高血压小鼠分为四组:对照组(仅给予标准饮食8周)、模型组(给予含8%氯化钠的饮食8周,在最后4周给予蒸馏水灌胃)、XJEK + 高盐处理组(给予含8%氯化钠的饮食8周,在最后4周给予XJEK灌胃)和厄贝沙坦 + 高盐处理组(给予含8%氯化钠的饮食8周,在最后4周给予厄贝沙坦灌胃)。然后检测高血压小鼠的血流动力学指标和心脏病理变化。使用主动脉环装置检测乙酰胆碱依赖性内皮舒张功能。采用比色分析法测定血清一氧化氮(NO)、超氧化物歧化酶活性和丙二醛含量;采用酶联免疫吸附测定法(ELISA)测量脑钠肽、血清血管紧张素II(Ang II)、内皮素-1含量和醛固酮;采用免疫组织化学法检测心脏组织中内皮型一氧化氮合酶(eNOS)、白细胞介素(IL)-1β、IL-10和肿瘤坏死因子(TNF)-α的表达。XJEK通过增强eNOS活性、促进NO生物利用度和降低血清Ang II含量,改善了心脏的收缩和舒张功能,改善了血流动力学参数和心血管重塑指标,减轻了心脏病理变化并改善了内皮功能障碍(ED)。此外,XJEK治疗抑制了心脏组织中IL-1β和TNF-α表达的增加以及IL-10表达的降低,并改善了氧化应激状态。因此,XJEK通过改善ED、恢复促炎和抗炎因子平衡以及降低氧化应激,对高盐诱导的小鼠高血压和心血管重塑发挥了保护作用。