摘要
目的:通过附子大黄不同配伍层次对阳虚便秘的治疗作用及其作用机制研究,揭示中医药的配伍规律并为临床中药配伍的科学应用提供依据。
方法:采用山西白醋加活性炭冰水灌胃法复制阳虚便秘动物模型,进行模型动物的排便实验、小肠推进实验、结肠肌电实验、胃肠肽指标测定实验、肠病理检测实验以研究附子大黄饮片配伍、组分配伍治疗阳虚便秘的作用机制;采用KM乳鼠的结肠Cajal间质细胞(结肠ICC)研究附子大黄成分配伍对结肠ICC的作用机制。
结果:附子大黄饮片水煎剂按不同比例配伍对阳虚便秘模型动物的排便疗效优于单用附子或大黄,作用机制与其调节胃肠激素和肠神经递质的分泌有关。附子大黄组分配伍预防给药时,附子总碱与大黄总蒽醌2:1配伍和大黄结合型蒽醌1:1、2:1配伍对阳虚便秘模型大鼠均具有增效作用;附子大黄组分配伍治疗给药时,附子总碱与大黄总蒽醌1:2配伍对阳虚便秘模型大鼠的增效作用最优;其发挥温阳通便功效的作用机制与调控肠运动相关胃肠肽的分泌有关,主要与调节MTL、SS、AchE的水平有关。乌头碱、大黄素对KM乳鼠结肠ICC的最大毒性浓度和临界作用时间点分别为0.1%、1min、15min、30min、60min、120min、180min、240min,0.5%、1min、15min、30min,毒作用机制可能与其升高细胞内MDA含量、降低细胞介质中Na~+K~+-ATP酶活力和细胞内电解质含量有关;大黄素与最大毒性浓度的乌头碱按1:2配伍可拮抗乌头碱对结肠ICC的损伤,作用机制可能与其抗细胞生物膜的氧化损伤、保护细胞内环境和细胞的能量代谢有关。
结论:研究结果表明:预防给药时,附子总碱与大黄总蒽醌或与大黄结合型蒽醌2:1配伍对阳虚便秘的治疗作用最优,以“扶正”为主;治疗给药时,附子总碱与大黄总蒽醌1:2配伍对阳虚便秘的治疗作用最优,以“祛邪”为主。大黄素与最大毒性浓度的乌头碱按1:2配伍对结肠ICC具有减毒增效作用。
Objective:The aims of this article are to reveal the compatibility rules of traditional Chinese medicine(TCM),and to offer the basis for scientific application of Chinese drugs in the clinic according to the research of Radix aconiti lateralis preparata(RALP) and Radix et Rhizoma Rhei(RRR) in treating the syndrome of yang-deficiency and constipation(SYDC).
Methods:On the basis of establishing animal models with SYDC,through the experiments of excreting feces,observing alvine movement and colonic myoelectricity,determining intestine-pathology and correlative indexes to study effective mechanisms with the cut crude drug-compatibility,constituent-compatibility of RALP and RRR in treating SYDC.Selecting colon's interstitial cells of Cajal(CICC) of KM's suckling mouse to study active mechanisms of RALP and RRR' component-compatibility on CICC.
Results:The results indicated that the compatibility of RALP and RRR at different ratios in treating SYDC were better than single drug of both,whose effect mechanism might be related to the content changes of gastrointestinal hormones and nervous transmitters;At the prophylactic administration drug,the compatibility of both total alkaloid of RALP and RRR's total anthraquinone in ratio of 2:1 and the total alkaloid of RALP and RRR's conjunct anthraquinone in ratios of 2:1 and 1:1 had effect on synergizing action;However,at the therapeutic administration drug,the compatibility of the total alkaloid of RALP and RRR's total anthraquinone in ratio of 1:2 was optimal in synergizing effect.The effective mechanisms of the compatibility among components in curing SYDC might be related to the content changes of MTL,SS and AchE in blood plasma.Aconitine and emodin are toxic to CICC, maximal toxicity dose and critical time of both were 0.1%,1min,15min,30min, 60min,120min,180min,240min;0.5%,1min,15min,30min.The compatibility ratio(2:1) of aconitine and emodin had effectiveness in decreasing aconitine's toxicity.Probably,the active mechanisms were inhibiting cell membrane's damnification,the debaser of the livingness of Na~+K~+-ATPase and the content of Ca~(2+) that lead by aconitine.
Conclusions:This study shows that the optimal ratio of the compatibility of the total alkaloid of RALP and RRR's total and conjunct anthraquinone in treating SYDC at the prophylactic administration drug and therapeutic administration drug are respectively 2:1 and 1:2.This study also shows that the compatibility of aconitine and emodin(2:1)has effect on CICC's decreasing toxicity and improving action.
引文
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