大川芎方对两肾一夹型高血压大鼠的压力反射敏感性和孤束核γ氨基丁酸能系统的影响  

Effects of Dachuanxiong(大川芎)Decoction on Baroreflex Sensitivity andγ-Aminobutyric Acidergic System in Nucleus Tractus Solitarii of Two-Kidney One-Clip Hypertensive Rats

作　　者：张琪[1,2] 李浩 赵珊 谭颖颖 ZHANG Qi;LI Hao;ZHAO Shan;TAN Yingying(Basic Medical College of Shaanxi University of Chinese Medicine,Xianyangg 712046;Shaanxi Provincial Key Laboratory of Traditional Chinese Medicine Encephalopathy,Xianyang 712046)

机构地区：[1]陕西中医药大学基础医学院,咸阳712046 [2]陕西省中医脑病学重点实验室,咸阳712046

出　　处：《中药药理与临床》2025年第2期2-7,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:82074380、81774295)。

摘　　要：目的:观察大川芎方对两肾一夹型(two-kidney one-clip,2K1C)高血压模型大鼠的异常交感神经活性、压力反射敏感性、脑内神经递质水平、以及孤束核内γ氨基丁酸(GABA)信号系统的表达和功能的影响。方法:经左肾动脉放置U型银夹的雄性SD大鼠,建立2K1C高血压模型。并随机分为正常对照组、模型对照组、大川芎方2.5、5 g/kg组和氯沙坦5 mg/kg组。无创血压系统测量清醒大鼠尾动脉血压;HE染色观察心肾组织病理变化;电生理记录肾交感神经活动(RSNA);ELISA法检测血浆去甲肾上腺素(NE)含量;Smyth法评估压力反射敏感性;荧光或化学发光法检测脑脊液GABA、谷氨酸水平以及孤束核谷氨酸脱羧酶(GAD)活性;Western blot法分析孤束核GABA_A受体、GABA_B受体、GAD65和GAD67表达;微注射法评价孤束核GABA_B受体功能。结果:与正常对照组比较,模型对照组的平均动脉压显著升高,出现心肾组织损伤,肾交感神经活动显著增加,血浆NE含量显著升高,压力敏感性指数显著降低,脑脊液GABA含量显著降低,谷氨酸含量显著升高,孤束核GABA_B受体表达显著上调,微注射CGP-35348或baclofen诱发的心血管效应显著增强,孤束核GAD67表达和GAD活性显著降低(P<0.01);与模型对照组比较,大川芎方2.5、5 g/kg组大鼠的平均动脉压明显降低,心肾组织损伤减轻,肾交感神经活动明显减少,血浆NE含量明显降低,压力敏感性指数明显增高,脑脊液GABA含量明显增加,谷氨酸含量明显降低,孤束核GABA_B受体表达明显降低,微注射CGP-35348或Baclofen诱发的心血管效应明显减弱,孤束核GAD67表达和GAD活性明显增加(P<0.05)。结论:大川芎方可以降低2K1C高血压模型的动脉血压及早期靶器官损伤、减弱异常交感神经活性和增强压力感受敏感性,该效应可能与其改善脑脊液神经递质GABA和谷氨酸水平、并调节孤束核内GABA_B受体和谷氨酸脱羧酶(GAD67)的表达和功能相�Objective:To observe the effects of Dachuanxiong(大川芎)Decoction on the abnormal sympathetic activity,baroreflex sensitivity,and neurotransmitter levels in the brain and the expression and function of theγ-aminobutyric acid(GABA)signaling system in the nucleus tractus solitarii of two-kidney one-clip(2K1C)hypertensive rats.Methods:The model of 2K1C hypertension was established in male SD rats by pla-cing a U-shaped silver clip through the left renal artery.Rats were randomized into normal control,model control,Dachuanxiong Decoction(5 g/kg and 2.5 g/kg),and losartan(5 mg/kg)groups.A non-invasive blood pressure system was used to measure the tail artery blood pres-sure of conscious rats.The pathological changes in the heart and kidney tissue were observed by hematoxylin-eosin staining.The renal sympa-thetic nerve activity(RSNA)was recorded by electrophysiology.The plasma norepinephrine content was determined by enzyme-linked immu-nosorbent assay.The baroreflex sensitivity was evaluated by the Smyth method.The levels of GABA and glutamate in the cerebrospinal fluid and the activity of glutamate decarboxylase(GAD)in the nucleus tractus solitarii were detected by the fluorescence or chemiluminescence assay.The protein levels of GABAA,GABAB,GAD65,and GAD67 in the nucleus tractus solitarii were determined by Western blotting.The function of GABAB in the nucleus tractus solitarii was evaluated by the microinjection method.Results:Compared with the normal control group,the model control group showed increased mean arterial pressure,appearance of heart and kidney injuries,enhanced RSNA,risen plasma NE level,de-creased baroreflex sensitivity index,and lowered GABA level and elevated glutamate level in the cerebrospinal fluid.In addition,the model con-trol group showed up-regulated expression of GABAB in the nucleus tractus solitarii,enhanced cardiovascular effect induced by microinjection of CGP-35348 or baclofen,and down-regulated expression of GAD67 and weakened GAD activity in the nucleus tractus solitarii(P<0.01).

关 键 词：大川芎方 高血压 交感神经 γ氨基丁酸能系统 孤束核 

分 类 号：R285.5[医药卫生—中药学]