Chen Ming, Chen Zhi-Wu, Long Zi-Jiang, Wang Ju-Tao, Wang Ya-Juan, Liu Jin-Lin
Department of Pharmacology, Anhui Medical University, Hefei, 230032, China.
Chin J Integr Med. 2015 Jan;21(1):36-42. doi: 10.1007/s11655-013-1464-0. Epub 2013 Jun 15.
To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms.
Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining.
Thirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P<0.05 or P<0.01). With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly.
Our findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang II and AT1R.
探讨无患子皂苷对自发性高血压大鼠的保护作用及其可能的细胞和分子机制。
将32只16周龄的自发性高血压大鼠随机分为四组（每组8只）：模型组（安慰剂）、阳性对照组（27 mg/kg卡托普利片）、无患子皂苷组（分别为27 mg/kg和108 mg/kg）。另取8只健康的Wistar-Kyoto品系（WKY）大鼠作为正常组。动物接受治疗8周。用无创血压计（BP-6）测定大鼠血压。此外，采用酶联免疫吸附测定法（ELISA）测定血浆和心肌组织中血管紧张素II（Ang II）的含量，采用定量实时聚合酶链反应（qRT-PCR）测定主动脉中血管紧张素1型受体（AT1R）的基因表达。采用免疫组织化学染色法测定心脏中转化生长因子-β1（TGF-β1）和AT1R的蛋白表达。采用蛋白质印迹法测定p38丝裂原活化蛋白激酶（p-p38MAPK）的磷酸化蛋白表达。采用放射免疫测定法测定血清中白细胞介素（IL）-1、IL-6和肿瘤坏死因子（TNF）的含量。并用苏木精-伊红（HE）或Masson染色对主动脉和心脏组织样本的组织病理学和形态学变化进行半定量评估。
单次或连续治疗30分钟后，无患子皂苷组的收缩压（SBP）显著降低。血清中AngII、IL-1、IL-6和TNF-α的含量、AT1R mRNA、p-p38MAPK和TGF-β1的表达均呈剂量依赖性显著抑制（P<0.05或P<0.01）。经无患子皂苷治疗后，与模型组相比，心脏和主动脉的病理变化明显改善。
我们的研究结果表明，无患子皂苷可能对自发性高血压大鼠具有保护作用，其细胞和分子机制可能与基于激活的Ang II和AT1R的p-p38MAPK信号通路介导的炎症反应调节有关。
