柴归汤调控环磷酸腺苷/蛋白激酶B信号通路干预原发性高血压大鼠作用机制  

Mechanism of Chaigui decoction’s modulation of cAMP/AKT signaling pathway in intervening blood pressure in spontaneously hypertensive rats

作　　者：许欣颖 胡小海 朱红俊[2] XU Xinying;HU Xiaohai;ZHU Hongjun(Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]南京中医药大学无锡附属医院,江苏无锡214071

出　　处：《陕西中医》2024年第3期313-317,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局第五批全国中医临床优秀人才研修项目[国中医药人教函(2022)1号];江苏省卫生健康委员会高层次卫生人才“六个一工程”拔尖人才项目[LGY2020025(A类)];江苏省无锡市“双百”中青年医疗卫生拔尖人才项目(BJ2020064)。

摘　　要：目的:探讨柴归汤对原发性高血压大鼠环磷酸腺苷(cAMP)/蛋白激酶B(AKT)通路表达的影响,分析其降压机制。方法:Wistar-Kyoto大鼠作为空白组。将原发性高血压大鼠随机分为模型组、贝那普利组,柴归汤入肠成分组、柴归汤高剂量组、柴归汤中剂量组、柴归汤低剂量组,并进行对应药物的灌胃治疗。给药28 d,检测各组大鼠血压;采用酶联免疫吸附测定法检测大鼠血清中cAMP水平及主动脉组织蛋白激酶B(AKT)、蛋白激酶A(PKA);应用PEX100磷酸化抗体芯片进行磷酸化检测分析。结果:给药后,柴归汤高剂量组、柴归汤中剂量组、柴归汤低剂量组、柴归汤入肠成分组及贝那普利组在干预4周后的收缩压、舒张压均降低(P<0.01)。与空白组相比,柴归汤入肠成分组cAMP、柴归汤低剂量组、柴归汤中剂量组PKA及贝那普利组AKT均有所升高(均P<0.05)。与模型组相比,柴归汤入肠成分组血清cAMP水平,柴归汤高剂量组、柴归汤中剂量组主动脉组织AKT水平,柴归汤中剂量组主动脉组织PKA水平均升高(均P<0.05)。结论:柴归汤可降低原发性高血压大鼠血压,上调大鼠血清cAMP、主动脉组织AKT、PKA水平,其降压机制可能与cAMP/AKT、cAMP/PKA级联介导信号相关。Objective:To investigate effect of Chaigui decoction on expression of cyclic adenosine monophosphate(cAMP)/protein kinase B(AKT)pathway,thus mechanism of lowering blood pressure.Methods:Wistar-Kyoto rats were used as blank group.Spontaneously hypertensive(SH)rats were randomly divided into model group,Benadryl group,Chaigui decoction intestinal component group,high-dose Chaigui decoction group,medium-dose Chaigui decoction group,low-dose Chaigui decoction group,which were treated with corresponding medication in the gastric gavage.The blood pressure of each group were measured after28 days of administration.cAMP level in serum,AKT and protein kinase A(PKA)levels in aortic tissues were detected by ELISA.Phosphorylation was detected by PEX100 phosphorylation antibody microarray.Results:AfteRdosing 4 weeks,the high-dose Chaigui decoction group,the medium-dose Chaigui decoction group,and the low-dose Chaigui decoction group,the Chaigui decoction intestinal component group,and the Benadryl group were significantly reduced systolic and diastolic blood pressures(P<0.01).Compared with the blank group,cAMP in the Chaigui decoction intestinal component group,PKA in the low-dose Chaigui decoction group and middle-dose Chaigui decoction group and AKT in the Benadryl group were all increased(all P<0.05).Compared with the model group,the cAMP level in the Chaigui decoction intestinal component group,the level of AKT in the aortic tissues of the high-dose Chaigui decoction group and middle-dose Chaigui decoction group,and the PKA level in the aortic tissues of the middle-dose group Chaigui decoction were all increased(all P<0.05).Conclusion:Chaigui decoction can reduce blood pressure,upregulate cAMP level in serum,and AKT、PKA levels in aortic tissues of SH rats.Its antihypertensive mechanism may be related to cAMP/AKT and cAMP/PKA cascade mediated signals.

关 键 词：高血压 柴归汤 环磷酸腺苷 蛋白激酶B 蛋白激酶A 一氧化氮合酶 

分 类 号：R544.1[医药卫生—心血管疾病]