中药药理与临床2025，Vol.41Issue(2)：2-7,6.
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 and γ-Aminobutyric Acidergic System in Nucleus Tractus Solitarii of Two-Kidney One-Clip Hypertensive Rats
摘要
Abstract
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 the γ-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).Com-pared with the model control group,Dachuanxiong Decoction(5 g/kg and 2.5 g/kg)groups showed declined mean arterial pressure,alleviated heart and kidney injuries,attenuated RSNA,lowered plasma NE level,and increased baroreflex sensitivity index.Additionally,Dachuanxiong De-coction elevated the GABA level and lowered the glutamate level in the cerebrospinal fluid,down-regulated the GABAB expression in the nucleus tractus solitarii,weakened the cardiovascular effect induced by microinjection of CGP-35348 or baclofen(P<0.05),and up-regulated the GAD67 expression and enhanced the GAD activity in the nucleus tractus solitarii(P<0.05).Conclusion:Dachuanxiong Decoction can lower arterial blood pressure and alleviate target organ damage in early stage,attenuate abnormal sympathetic nerve activity and enhance baroreflex sen-sitivity in the rat model of 2K1C hypertension.It may exert the effects above by elevating the GABA and glutamate levels in the cerebrospinal fluid and regulating the expression of GABAB and GAD67 in the nucleus tractus solitarii.This study provides new evidence for exploring the mechanism of Dachuanxiong Decoction in preventing and treating hypertension by regulating the nervous system function.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Key words
Dachuanxiong(大川芎)Decoction/Hypertension/Sympathetic nerve/γ-Aminobutyric acidergic system/Nucleus tractus solitarii引用本文复制引用
张琪,李浩,赵珊,谭颖颖..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[J].中药药理与临床,2025,41(2):2-7,6.基金项目
国家自然科学基金项目(编号:82074380、81774295). （编号:82074380、81774295）
