天丹降压方对自发性高血压肝阳上亢模型大鼠的影响

Effect of Tiandan Jiangya prescription on a rat model of spontaneous hypertension with syndrome of upper hyperactivity of liver Yang

目的:探讨天丹降压方对自发性高血压大鼠(SHR)肝阳上亢证模型的影响。方法:将60只SHR随机分为SHR对照组、SHR模型组、坎地沙坦酯组及天丹降压方低、中、高剂量组,每组各10只,另将10只正常血压(WKY)大鼠设为空白对照组。空白对照组、SHR对照组予蒸馏水干预12周,其余组大鼠采用静脉推注参附注射液的方法制备肝阳上亢证模型。造模成功后进行相应药物干预,剂量均为8 ml/kg,SHR模型组灌胃蒸馏水,连续8周。比较各组大鼠24 h饮水量、易激惹程度、眼结膜充血情况、痛阈感觉温度、收缩压、Toll样受体4(TLR4)、核因子-κB(NF-κB)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)等各项指标情况。结果:SHR各造模组的24 h饮水量、易激惹程度、眼结膜充血情况、痛阈感觉温度、收缩压造模前后组内比较,差异均有统计学意义(P<0.01);造模后,SHR造模组的上述5项指标分别与空白对照组、SHR对照组比较,差异均有统计学意义(P<0.01)。干预前,SHR对照组、SHR模型组及各药物组的收缩压与空白对照组比较,SHR模型组及各药物组的收缩压与SHR对照组比较,差异均有统计学意义(P<0.05);干预第12、24、36、48、60天,各药物组的收缩压与SHR模型组比较,差异均有统计学意义(P<0.05)。各组血浆TLR4、NF-κB、IL-6、TNF-α含量比较,SHR模型组均高于空白对照组及SHR对照组,各药物组均低于SHR模型组,差异均有统计学意义(P<0.01)。结论:天丹降压方对SHR肝阳上亢证模型大鼠有明显的降压作用,并可降低其血浆TLR4、NF-κB、TNF-α、IL-6含量,其作用机制可能与干预TLR4/NF-κB通路相关。

Objective:To investigate the effect of Tiandan Jiangya prescription on a spontaneously hypertensive rat(SHR)model of syndrome of upper hyperactivity of liver Yang.Methods:A total of 60 SHRs were randomly divided into SHR control group,SHR model group,candesartan cilexetil group,and low-,middle-,and high-dose Tiandan Jiangya prescription groups,with 10 rats in each group,and another 10 WKY rats with normal blood pressure were selected as blank control group.The rats in the blank control group and the SHR control group were given distilled water for 12 weeks,and the rats in the other groups were given intravenous injection of Shenfu injection to establish a model of syndrome of upper hyperactivity of liver Yang.Corresponding drug intervention was given after successful modeling at a dose of 8 ml/kg,and the rats in the SHR model group were given distilled water by gavage,for 8 consecutive weeks.The above groups were compared in terms of 24-hour water consumption,degree of irritability,conjunctival hyperemia,pain threshold temperature,systolic pressure,Toll-like receptor 4(TLR4),nuclear factor-kappa B(NF-κB),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α).Results:SHR modeling groups had significant changes in 24-hour water consumption,degree of irritability,conjunctival hyperemia,pain threshold temperature,and systolic pressure after modeling(P<0.01),and after modeling,there were significant differences in these five indices between the SHR modeling groups and the blank control group,as well as between the SHR modeling groups and the SHR control group(P<0.01).Before intervention,there was a significant difference in systolic pressure between the blank control group and the other groups,as well as between the SHR model group/the medication groups and the SHR control group(P<0.05),and on days 12,24,36,48,and 60 of intervention,there was a significant difference in SHR between the medication groups and the SHR model group(P<0.05).The SHR model group had significantly higher plasma levels of TLR4,NF-κB,IL-6,and TNF-αthan the blank control group and the SHR control group,and the medication groups had significantly lower levels than the SHR model group(P<0.01).Conclusion:Tiandan Jiangya prescription has a significant antihypertensive effect on SHR model of syndrome of upper hyperactivity of liver Yang and can reduce the plasma levels of TLR4,NF-κB,TNF-α,and IL-6,possibly by intervening against the TLR4/NF-κB signaling pathway.