红景天苷对Ang Ⅱ诱导的小鼠模型高血压作用的研究

Effect of salidroside on hypertension induced by angiotensin Ⅱ in mouse model

目的 探讨红景天苷对血管紧张素2(Ang Ⅱ)诱导的小鼠模型血压是否有变化以及其影响的机制。方法 将成年雄性C57/B6小鼠随机分为五组,对照组5只小鼠,另外四组各8只小鼠,利用Ang Ⅱ诱导血压升高,2周后其中三组高血压小鼠分别接受20 mg/kg、40 mg/kg以及80 mg/kg剂量的红景天苷治疗;利用免疫组化的方法分析各组小鼠脑干室旁核(PVN)及延髓头端腹外侧脑区(RVLM)小胶质细胞的激活状态;利用酶联免疫吸附试验观察各组小鼠上述两个脑区内炎性因子白介素1β(IL-1β)及肿瘤坏死因子α(INF-α)的表达量。结果 20 mg/kg以及80 mg/kg剂量的红景天苷并无改善高血压的进程,而40 mg/kg剂量在第24天以及第28天显著缓解了血压的上升;给予40 mg/kg红景天苷治疗的高血压小鼠PVN及RVLM脑区内的小胶质细胞体积较未治疗组体积减少,突起变少,显著下调了小胶质细胞的激活状态;另外40 mg/kg红景天苷治疗组的高血压小鼠两个脑区炎性因子IL-1β及INF-α的表达量都明显下降。结论 红景天苷可能通过抑制小胶质细胞的激活及高血压后神经炎症反应从而达到缓解高血压的作用。

Objective To investigate the effect of salidroside on hypertension induced by angiotensin Ⅱ(Ang Ⅱ) in mouse model, and its mechanism. Methods Adult male C57/6J mice were randomly divided into 5 groups, five mice in the control group, eight mice in other 4 groups, in which mice were induced hypertension by using Ang Ⅱ. After 2 weeks, 3 groups of hypertensive mice separately received retreatment of 20 mg/kg, 40 mg/kg and 80 mg/kg doses of salidroside. Immunohistochemical method was used to analyze the activation status of microglia in the brainstem paraventricular nucleus(PVN) and brainstem of the rostroventrolateral medulla(RVLM) of each group. The expression levels of inflammatory factors interleukin-1β(IL-1β) and tumor necrosis factor(TNF)-α in the above two brain regions of mice in each group were observed by enzyme-linked immunosorbent assay. Results 20 mg/kg and 80 mg/kg dose of salidroside did not improve the progression of hypertension, but the dose of 40 mg/kg significantly relieved the rise in blood pressure on day 24 and 28. The volume of microglia in the brain regions of PVN and RVLM in hypertensive mice treated with 40 mg/kg salidroside was reduced compared with the untreated group, and the number of neurites decreased, which significantly downregulated the activation of microglia. In addition, the expression levels of inflammatory factors IL-1β and TNF-α in the two brain regions of hypertensive mice treated with salidroside significantly decreased.Conclusions Salidroside may achieves the effect of relieving hypertension by inhibiting the activation of microglia and the neuroinflammatory reaction after hypertension.