■注意缺陷多动障碍(ADHD),儿童普遍存在的神经发育障碍,可以通过中药制剂龙目清心合剂(LMQXM)有效缓解,但其机制尚未完全阐明。
■研究LMQXM改善自发性高血压大鼠(SHR/NCrl)行为的潜在药理机制。
■将SHR/NCrl大鼠随机分为模型(SHR)组,盐酸哌醋甲酯(MPH)组,和接受不同剂量的LMQXM的组进入具有临床有效剂量的中等剂量(MD)组,低剂量(LD)组是临床有效剂量的0.5倍,高剂量(HD)组是临床有效剂量的2倍。此外,以WKY/NCrl大鼠为对照组。行为评价涉及露天试验和Morris水迷宫试验。HPLC,LC-MS,ELISA,免疫组织化学,蛋白质印迹,和RT-qPCR用于仔细检查儿茶酚胺神经递质含量以及与多巴胺受体D1(DRD1)/cAMP/蛋白激酶A(PKA)-cAMP反应元件结合(CREB)相关的蛋白质和基因的表达在前额叶皮层(PFC)和纹状体。
■MPH和LMQXM改善SHR/NCrl大鼠多动症和学习记忆障碍。其中,LMQXM-MD和MPH也上调多巴胺(DA),去甲肾上腺素(NE),腺苷酸环化酶(AC)和cAMP水平,以及与DRD1/cAMP/PKA-CREB通路相关的蛋白和基因在SHR/NCrl大鼠PFC和纹状体中的表达。LMQXM-LD组的PFC和纹状体DA水平也上调,LMQXM-HD组的纹状体DA水平也上调,但与SHR组相比,其NE水平无统计学差异。LMQXM-LD和LMQXM-HD也上调一些DRD1/cAMP/PKA-CREB通路相关蛋白和基因表达,但在PFC和纹状体中效果明显不同。经过综合分析,LMQXM-MD似乎是最有效的剂量。
■我们的研究初步表明,LMQXM可以通过升高PFC和纹状体中的儿茶酚胺神经递质来纠正SHR/NCrl大鼠的多动症和学习记忆障碍。这种效应可能归因于DRD1/cAMP/PKA-CREB信号通路的潜在激活,在中等剂量下似乎达到最佳反应。
UNASSIGNED: Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, can be effectively alleviated by the herbal preparation Long Mu Qing Xin Mixture (LMQXM), but its mechanism has not been fully elucidated.
UNASSIGNED: To scrutinize the potential pharmacological mechanisms by which LMQXM improves behavior in spontaneously hypertensive rats (SHR/NCrl).
UNASSIGNED: The SHR/NCrl rats were randomly stratified into the model (SHR) group, the methylphenidate hydrochloride (MPH) group, and groups subjected to varying dosages of LMQXM into the medium dose (MD) group with a clinically effective dose, the low dose (LD) group with 0.5 times the clinically effective dose, and high dose (HD) group with 2 times the clinically effective dose. Furthermore, the WKY/NCrl rats constituted the control group. The evaluation of behavior involved the open field test and the Morris water maze test. HPLC, LC-MS, ELISA, immunohistochemistry, Western blot, and RT-qPCR were utilized to scrutinize the catecholamine neurotransmitter content and the expression of proteins and genes associated with the dopamine receptor D1 (DRD1)/cAMP/protein kinase A (PKA)-cAMP response element-binding (CREB) pathway in prefrontal cortex (PFC) and striatum.
UNASSIGNED: MPH and LMQXM ameliorated hyperactivity and learning and memory deficits of SHR/NCrl rats. Among them, LMQXM-MD and MPH also upregulated dopamine (DA), norepinephrine (NE), adenylate cyclase (AC) and cAMP levels, and the expression of proteins and genes associated with the DRD1/cAMP/PKA-CREB pathway in PFC and striatum of SHR/NCrl rats. PFC and striatum DA levels were also upregulated in the LMQXM-LD group as well as the striatum DA levels in the LMQXM-HD group, but there were no statistically significant differences in their NE levels compared to the SHR group. LMQXM-LD and LMQXM-HD also upregulated some DRD1/cAMP/PKA-CREB pathway-related proteins and gene expression, but the effects were discernibly disparate in PFC and striatum. Upon comprehensive analysis, LMQXM-MD appeared to be the most effective dose.
UNASSIGNED: Our study tentatively suggests that LMQXM may rectify hyperactivity and learning and memory deficits of SHR/NCrl rats by elevating catecholamine neurotransmitters in the PFC and striatum. This effect may be attributed to the potential activation of the DRD1/cAMP/PKA-CREB signaling pathway, which appears to achieve an optimal response at moderate doses.