中药复方速回初压肽通过PI3K/Akt/eNOS通路对SHR大鼠内皮功能障碍的影响

Effects of SHCY peptide on endothelial dysfunction in SHR rats through PI3K/Akt/eNOS pathway

目的 探讨中药复方速回初压肽通过PI3K/Akt/eNOS信号通路对高血压大鼠的胸主动脉血管内皮的保护作用。方法 将35只15周龄的雄性SHR大鼠随机分为5组:模型组、速回初压肽低、中、高剂量组、培哚普利组,每组7只;以7只同龄的Wistar大鼠作为正常组。无创血压检测系统检测给药前和给药后各组大鼠尾动脉收缩压和舒张压;超声心动图检测各组大鼠的心脏结构的变化;HE染色观察各组大鼠的胸主动脉病理变化;ELISA检测各组大鼠血清中的AngⅡ、ET-1和NO;Western Blot检测各组大鼠胸主动脉的PI3K、p-PI3K、Akt、p-Akt、eNOS、p-eNOS蛋白表达。结果 给药8周后,速回初压肽低、中、高剂量组,培哚普利组大鼠收缩压和舒张压均低于模型组(P<0.05)。超声心动图结果显示,与模型组相比,速回初压肽中、高剂量组,培哚普利组的收缩末期左心室内径(LVIDs)、舒张末期左心室内径(LVIDd)、舒张末期左心室前壁的厚度(LVAWd)和舒张末期左心室后壁厚度(LVPWd)均显著降低(P<0.05)。HE结果显示,与模型组相比,速回初压肽中、高剂量组和培哚普利组大鼠的肿胀的内皮细胞得到改善,血管内皮趋于平滑。ELISA结果表明,与模型组比,速回初压肽中、高剂量组和培哚普利组血清中的NO含量显著升高(P<0.05),Ang II、ET-1含量均显著降低(P<0.05)。Western Blot结果表明,与模型组相比,速回初压肽中、高剂量组和培哚普利组的大鼠胸主动脉中的p-PI3K/PI3K、p-Akt/Akt、p-eNOS/eNOS的蛋白表达水平显著上升。结论 中药复方速回初压肽可能通过影响PI3K/Akt/eNOS信号通路促进NO的释放,降低Ang II、ET-1的水平,改善SHR大鼠的内皮功能障碍,对SHR大鼠的血压具有显著的干预作用。

Objective To investigate the protective effect of traditional Chinese medicine compound SHCY peptide on the vascular endothelium of hypertensive rats through the PI3K/Akt/eNOS pathway.Methods Thirty-five 15-week-old male SHR rats were randomly divided into 5 groups:model group,perindopril group,and low,medium,and high dose groups of the SHCY peptide,each group of seven.Seven Wistar rats of the same age were selected as the normal group.The non-invasive blood pressure detection system measured the artery systolic and diastolic blood pressure of the tail arteries of rats in each group before and after intragastric administration.Echocardiography was performed to examine the changes of heart structure in each group.HE staining was used to observe the pathological changes of the thoracic aorta in each group;Enzyme linked immunosorbent assay(ELISA)was used to detect levels of angiotensin Ⅱ(Ang Ⅱ),endothelin-1(ET-1),nitric oxide(NO);Western Blot was used to detect the protein expression of phosphatidylinositol 3-kinase(PI3K),phosphorylated phosphatidylinositol 3-kinase(p-PI3K),protein kinase B(Akt),phosphorylated protein kinase(p-Akt),endothelial nitric oxide synthase(eNOS)and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein expression.Results After 8 weeks of administration,the systolic blood pressure of rats in the low,medium,and high dose groups of the SHCY peptide and the perindopril group were lower than those in the model group(P<0.05).The echocardiographic results showed that compared with the model group,the end-systolic left ventricular diameter(LVIDs),end-diastolic left ventricular diameter(LVIDd),end-diastolic left ventricular anterior wall thickness(LVAWd)and end-diastolic left ventricular posterior wall thickness(LVPWd)of SHCY peptide group and perindopril group were significantly reduced(P<0.05).The HE results showed that compared with the model group,the swelling endothelial cells in the rats treated with the SHCY peptide group and perindopril group was improved,and the arrangement of vascular endothelial cells tended to be smooth.ELISA results showed that compared with the model group,the serum NO content in the perindopril group,the middle and high dose groups of the SHCY peptide were significantly increased(P<0.05),while Ang Ⅱ,ET-1 contents in the serum were significantly reduced(P<0.05).Western Blot results showed a significantly increase in protein expression levels of p-PI3K/PI3K,p-Akt/Akt,and p-eNOS/eNOS.Conclusion The traditional Chinese medicine compound SHCY peptide may promote the release of NO by affecting the PI3K/Akt/eNOS signaling pathway,reduce the levels of Ang Ⅱ,ET-1,improve endothelial function injury in SHR,and have a significant intervention effect on blood pressure in SHR.