天丹降压方对自发性高血压肝阳上亢模型大鼠的影响_陶源.pdf

引用:陶源，胡旦，王国庆，卿媛媛，朱筱婧，颜旭天丹降压方对自发性高血压肝阳上亢模型大鼠的影响 J 湖南中医杂志，2023，39(1):163167.天丹降压方对自发性高血压肝阳上亢模型大鼠的影响陶源1，胡旦1，王国庆1，卿媛媛1，朱筱婧2，颜旭2(1.湖南中医药大学，湖南长沙，410208;2.湖南省中医药研究院附属医院，湖南长沙，410006)摘要 目的:探讨天丹降压方对自发性高血压大鼠(SH)肝阳上亢证模型的影响。方法:将 60 只SH 随机分为 SH 对照组、SH 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、SH 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，SH 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(TL4)、核因子B(NFB)、白细胞介素6(IL6)及肿瘤坏死因子(TNF)等各项指标情况。结果:SH 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(P0.01);造模后，SH 造模组的上述 5 项指标分别与空白对照组、SH 对照组比较，差异均有统计学意义(P0.01)。干预前，SH 对照组、SH 模型组及各药物组的收缩压与空白对照组比较，SH 模型组及各药物组的收缩压与 SH 对照组比较，差异均有统计学意义(P0.05);干预第 12、24、36、48、60 天，各药物组的收缩压与 SH 模型组比较，差异均有统计学意义(P0.05)。各组血浆TL4、NFB、IL6、TNF 含量比较，SH 模型组均高于空白对照组及 SH 对照组，各药物组均低于 SH 模型组，差异均有统计学意义(P0.01)。结论:天丹降压方对 SH 肝阳上亢证模型大鼠有明显的降压作用，并可降低其血浆 TL4、NFB、TNF、IL6 含量，其作用机制可能与干预 TL4/NFB 通路相关。关键词 自发性高血压大鼠;肝阳上亢证;天丹降压方;实验研究 中图分类号 285.5 文献标识码 ADOI:1016808/jcnkiissn10037705202301039基金项目:湖南省教育厅科研项目(18C0381);湖南省中医药研究院科研项目(201813)第一作者:陶源，女，2020 级硕士研究生，研究方向:中医药防治心血管疾病通信作者:颜旭，男，医学博士，主任医师，硕士研究生导师，研究方向:中医药防治心血管疾病，Email:朱筱婧，女，医学硕士，副主任医师，研究方向:中医药防治心血管疾病，Email:471499219 Effect of Tiandan Jiangya prescription on a rat model of spontaneous hypertensionwith syndrome of upper hyperactivity of liver YangTAO Yuan1，HU Dan1，WANG Guoqing1，QING Yuanyuan1，ZHU Xiaojing2，YAN Xu2(1.Hunan University of Chinese Medicine，Changsha 410208，Hunan，China;2.The Affiliated Hospital of Hunan Academy of Chinese Medicine，Changsha 410006，Hunan，China)Abstract Objective:To investigate the effect of Tiandan Jiangya prescription on a spontaneously hypertensive rat(SH)model of syndrome of upper hyperactivity of liver Yang.Methods:A total of 60 SHs were randomly divided intoSH control group，SH model group，candesartan cilexetil group，and low，middle，and highdose Tiandan Jiangya pre-scription groups，with 10 rats in each group，and another 10 WKY rats with normal blood pressure were selected as blankcontrol group.The rats in the blank control group and the SH control group were given distilled water for 12 weeks，andthe rats in the other groups were given intravenous injection of Shenfu injection to establish a model of syndrome of upperhyperactivity of liver Yang.Corresponding drug intervention was given after successful modeling at a dose of 8 ml/kg，and361第 39 卷第 1 期2023 年 1 月HUNAN JOUNAL OF TADITIONAL CHINESE MEDICINEVol.39No.1Jan.2023the rats in the SH model group were given distilled water by gavage，for 8 consecutive weeks.The above groups were com-pared in terms of 24hour water consumption，degree of irritability，conjunctival hyperemia，pain threshold temperature，systolic pressure，Tolllike receptor 4(TL4)，nuclear factorkappa B(NFB)，interleukin6(IL6)，and tumor nec-rosis factor(TNF).esults:SH modeling groups had significant changes in 24hour water consumption，degree ofirritability，conjunctival hyperemia，pain threshold temperature，and systolic pressure after modeling(P0.01)，and aftermodeling，there were significant differences in these five indices between the SH modeling groups and the blank controlgroup，as well as between the SH modeling groups and the SH control group(P0.01).Before intervention，there was asignificant difference in systolic pressure between the blank control group and the other groups，as well as between the SHmodel group/the medication groups and the SH control group(P0.05)，and on days 12，24，36，48，and 60 of interven-tion，there was a significant difference in SH between the medication groups and the SH model group(P0.05).TheSH model group had significantly higher plasma levels of TL4，NFB，IL6，and TNF than the blank control groupand the SH control group，and the medication groups had significantly lower levels than the SH model group(P0.01).Conclusion:Tiandan Jiangya prescription has a significant antihypertensive effect on SH model of syndrome of upper hy-peractivity of liver Yang and can reduce the plasma levels of TL4，NFB，TNF，and IL6，possibly by intervening a-gainst the TL4/NFB signaling pathway.Keywords spontaneously hypertensive rat;syndrome of upper hyperactivity of liver yang;Tiandan Jiangya pre-scription;experimental study原发性高血压病的发病机制十分复杂，是一种以体循环动脉压增高为特征的常见心血管疾病，简称为高血压病1。天丹降压方是湖南省名老中医喻正科教授临床治疗高血压病肝阳上亢证的经验方，具有平肝潜阳、祛瘀化痰的作用。前期研究发现天丹降压方具有降压作用，并可以逆转高血压病左心室肥厚，保护靶器官，改善高血压病引起的头晕头痛等症状24。本实验将自发性高血压大鼠(SH)作为研究对象，构建肝阳上亢证模型，采用天丹降压方不同剂量进行干预，以探讨天丹降压方对 SH 大鼠肝阳上亢模型的影响及作用机制，为天丹降压方的临床应用提供实验依据。1实验材料1.1动物10 周龄 SPF 级雄性 SH 大鼠 60 只，体质量 250 280 g，SPF 级雄性正常血压 WistarKyoto(WKY)大鼠 10 只，均由湖南斯莱克景达实验动物有限公司提供，动物许可证编号:SCXK(湘)20160002。1.2药物1)天丹降压方:天麻12 g，丹参12 g，鬼箭羽 10 g，钩藤 10 g，珍珠母 12 g，地龙 10 g，山楂10 g，益母草 10 g，陈皮 10 g，茯苓 10 g，葛根 10 g，夏枯草 10 g。上述中药购于湖南省中医药研究院附属医院，由湖南中医药大学科技创新中心制备。以上中药采用蒸馏水浸泡 30 min，煎煮 2 次。将2 次药液混合后过滤，用 80负压旋转蒸馏浓缩至药物浓度分别为 4、2、1 g/ml。2)坎地沙坦酯混悬液(浙江永宁药业股份有限公司，批准文号:国药准字 H20080183，批号:2007173，规格:8 mg/片)。取坎地沙坦酯 8 mg 在乳钵中研磨，用蒸馏水配制80 ml混悬液，浓度为0.1 mg/ml。3)参附注射液(雅安三九药业有限公司，批准文号:国药准字Z20043117，规格:10 ml/支)。取参附注射液 20 ml，以 0.9%氯化钠注射液 250 ml 配置，药物浓度为8 ml/kg，用于造模。1.3