川乌与白蔹反药组合协同降低大鼠肾血流作用及机制研究

Synergistic reducing effect and mechanism of Aconitum carmichaelii and Ampelopsis japonica on renal blood flow

目的考察川乌与白蔹反药配伍对大鼠肾血流的影响,并基于β肾上腺素能受体(β-AR)和肾素-血管紧张素-醛固酮系统(RAAS)探讨其作用机制。方法在体实验选用60只健康SD大鼠随机分成6组:对照组、白蔹组、制川乌组、制川乌白蔹组、生川乌组及生川乌白蔹组,连续给药5 d后,采用激光多普勒血流仪测量肾血流,用放免法检测血浆肾素、血管紧张素和醛固酮水平。离体实验以β-AR为靶标,采用双荧光素酶报告基因技术评价川乌与白蔹反药组合对β-AR的激动作用。结果正常大鼠肾血流为(257±47)PU,生川乌能显著降低大鼠肾血流[(143±31)PU vs(257±47)PU,P<0.01],炮制后作用减弱;生/制川乌与白蔹配伍后作用均加强,生川乌配伍与单独生川乌比较肾血流显著下降[(105±33)PU vs(143±31)PU,P<0.05]。与生川乌单药相比,反药组合具有升高血浆RAAS的趋势,可显著升高AngⅡ[(394±8)pg·m L-1 vs(380±12)pg·m L-1,P<0.05];川乌有明显激动β-AR的作用,与白蔹反药配伍后β-AR激动作用进一步增强[(8.195±1.455)RUF ratio vs(4.896±0.802)RUF ratio,P<0.01]。结论乌头与白蔹反药组合可能通过增加肾脏β-AR激动作用调控RAAS水平,进一步降低肾血流。在疾病治疗过程中持续降低肾血流,加重肾损伤可能是川乌与白蔹"相反"的主要表现之一。

Objective To investigate whether the compatibility ofAconitum carmichaelii and Ampelopsisjapon- ica can influence the renal blood flow and the plasma levels of renin-angiotensin-aldosterone system （RAAS） in normal rats. Methods Totally 60 healthy SD rats were randomly divided into 6 groups with 10 in each group： a control （C） group, an Ampelopsisjaponica （A） group, a processed Radix Aconiti （P） group, an A ＋ P （AP） group, an unprocessed Radix Aconiti （U） group, and an A ＋ U （AU） group. After intragastric gavage for 5 days, the renal blood flow of each rat was tested by Laser Doppler flowmeter, and the plasma levels of renin, angio- tensin and aldosterone were measured by radioimmunoassay. The agonistic effect of compatibility of Aconitum carmichaelii and Ampelopsis japonica on β-adrenergic receptor （β-AR） was screened and evaluated systemati- cally through in vitro experiment. Results The renal blood flow （RBF） of normal rats was about （257±47） PU. RBF was reduced significantly in the U group [ （143±31） PU vs （257± 47） PU, P 〈 0.01 ], while the effect was decreased after the processing. In the AU group RBF was decreased and further compared with that of the U group [ （105±33） PU vs （143±31） PU, P 〈 0.05]. Meanwhile, in the U group the plasma level of RAAS was increased, and especially Ang I] concentration was elevated after combination with A [ （394± 8） pg · mL -1 vs （380± 12） pg· mL - 1 p 〈 0.05]. The U group had an obvious agonistic effect onβ-AR, and the effect was further enhanced after combination with A [ （8.195 ±1.455） RUF ratio vs （4.196±0.802） RUF ratio, P 〈 0.01]. Conclusion Compatibility of Ampelopsis japonica and unprocessed Radix Aconiti can further reduce the RBFin normal rats, possibly by increasing the agonistic action onβ-AR in the kidney and regulating the RAAS level, which may β one specific performance of compatibility of ＂ampelopsis attack aconitum＂.