摘要
目的研究复方钩藤降压片对TLR4/NF-κB信号通路以及血管紧张素Ⅱ(angiotensinⅡ, AngⅡ)、血管紧张素(1-7)[an-giotensin1-7, Ang(1-7)]、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1, MCP-1)相关炎症因子表达的影响,探讨复方钩藤降压片对自发性高血压大鼠(spontaneously hypertensire rats, SHR)的可能降压机制。方法将21只7周龄雄性SHR随机分为模型对照组(SHR组)、复方钩藤降压片治疗组(SHR-G组)、缬沙坦片治疗组(SHR-D组),另取7只雄性WKY大鼠为空白对照组(WKY组)。所有大鼠给予相应干预,6周后采用ELISA方法检测血清中AngⅡ、Ang(1-7)和MCP-1的含量;采用免疫组织化学方法检测胸主动脉内皮细胞中TLR4和NF-κB p65的蛋白水平。结果 (1)SHR组血浆促炎因子AngⅡ、MCP-1的含量明显高于WKY组(P<0.05),而抑炎因子Ang(1-7)的含量明显低于WKY组(P<0.01);经复方钩藤降压片和缬沙坦片干预,可以明显降低SHR血浆中AngⅡ和MCP-1的含量(P<0.05),而增加血浆抑炎因子Ang(1-7)的含量(P<0.05 or P<0.01)。(2)SHR组胸主动脉内皮细胞中TLR4和NF-κB p65的蛋白水平明显高于WKY组(P<0.01);相对于SHR组,SHR-D和SHR-G组大鼠胸主动脉组织中TLR4和NF-κB p65的表达量显著降低(P<0.05 or P<0.01)。结论复方钩藤降压片可通过抑制胸主动脉组织内皮细胞TLR4/NF-κB信号通路的活化,降低促炎因子AngⅡ、MCP-1的水平,提高抑炎因子Ang(1-7)的水平,抑制机体的炎症状态。
Objective To investigate the effect of Compound Gouteng Jiangya Tablet on the TLR4/NF-κB signaling pathway and the expression of angiotensinⅡ(AngⅡ)and angiotensin 1-7[Ang(1-7)],monocyte chemotactic protein-1(MCP-1)associated inflammatory cytokines and its possible antihypertensive mechanism in spontaneous hypertension rats(SHRs).Methods A total of 21 male SHRs aged 7 weeks were randomly divided into model control group(SHR group),Compound Gouteng Jiangya Tablet group(SHR-G group),and valsartan group(SHR-D group),and another 7 male WKY rats with the same age were selected as blank control group(WKY group).All rats were given the corresponding intervention,and 6 weeks later,ELISA was used to measure the serum levels of AngⅡ,Ang(1-7)and MCP-1,and immunohistochemistry was used to measure the protein expression of TLR4 and NF-κBp65 in thoracic aortic endothelial cells.Results Compared with the WKY group,the SHR group had significantly higher levels of the plasma proinflammatory factors AngⅡand MCP-1(P<0.05)and a significantly lower level of the anti-inflammatory cytokine Ang(1-7)(P<0.001).The treatment with Compound Gouteng Jiangya Tablet and valsartan significantly reduced the plasma levels of AngII and MCP-1 in SHRs(P<0.05)and significantly increased the plasma level of the anti-inflammatory cytokine Ang(1-7)(P<0.05).The SHR group had significantly higher protein levels of TLR4 and NF-κB p65 in thoracic aortic endothelial cells than the WKY group(P<0.01),and compared with the SHR group,the SHR-D and SHR-G groups had significant reductions in the expression of TLR4 and NF-κB p65 in thoracic aorta tissue(P<0.01).Conclusion Compound Gouteng Jiangya Tablet can inhibit inflammatory state in the body by inhibiting activation of the TLR4/NF-κB signaling pathway in thoracic aortic endothelial cells,reducing the levels of the proinflammatory factors AngⅡand MCP-1l,and increasing the level of the anti-inflammatory cytokine Ang(1-7).
作者
李霞
曾勇
张稳
LI Xia;ZENG Yong;ZHANG Wen(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410000,China)
出处
《湖南中医药大学学报》
CAS
2019年第2期168-172,共5页
Journal of Hunan University of Chinese Medicine
基金
国家自然科学基金项目(81473616)
湖南省高校创新平台开放基金项目(15K095)
湖南省中药粉体与创新药物省部共建国家重点实验室基金项目(ZYFT201503)
