目的 通过观察静灵口服液（JLOL）对注意缺陷多动障碍（ADHD）大鼠脑肠肽分泌及肠道菌群结构的影响，探讨其治疗ADHD的作用机制。方法 将40只SPF级3周龄雄性SHR大鼠随机分为模型组、盐酸托莫西汀（阳性药，2.68 mg·kg^-1）组及JLOL低、中、高剂量（2、4、8 mL·kg^-1）组，每组8只，并以8只同周龄雄性WKY大鼠作为对照组，各组大鼠ig给予相应药物，对照组和模型组ig给予去离子水，每天2次，给药21 d。实验期间记录大鼠体质量变化情况；旷场实验与水迷宫实验观察大鼠行为学变化；采用酶联免疫吸附（ELISA）法检测大鼠血清胃泌素（GAS）、胃动素（MTL）、饥饿素（GHRL）、血管活性肠肽（VIP）、P物质（SP）、5-羟色胺（5-HT）含量；宏基因组学检测大鼠肠道菌群的结构变化。结果 与模型组相比，JLOL组大鼠体质量显著降低（P＜0.05）；旷场实验运动总路程、中心区域时间显著降低（P＜0.05、0.01），静止时间、边缘区域时间显著升高（P＜0.05、0.01、0.001）；水迷宫实验潜伏时间均明显缩短（P＜0.05、0.01、0.001）；血清GAS、MTL、SP、GHRL水平显著升高（P＜0.05、0.001），VIP、5-HT水平显著降低（P＜0.05、0.01）；肠道菌群物种多样性明显提高，厚壁菌门（Firmicutes）丰度明显升高，拟杆菌门（Bacteroidota）丰度明显下降，拟杆菌属（Bacteroides）、双歧杆菌属（Bifidobacterium）、粪杆菌属（Faecalibacterium）、副拟杆菌属（Parabacteroides）相对丰度上调，梭菌属（Clostridium）、肠杆菌属（Enterobacter）、瘤胃球菌属（Ruminococcus）相对丰度下调； Chao1、Simpson、Observed、Shannon指数均有所上升（P＜0.05、0.01、0.001）。Ruminococcus、Enterobacter与血清中GAS、MTL、GHRL、SP含量呈负相关，与血清中VIP、5-HT含量呈正相关； Faccalibacterium、Parabacteroides、Bifidobacterium、Bacteroides与血清中GAS、MTL、GHRL、SP呈正相关，与血清中VIP、5-HT含量呈负相关。结论 JLOL对ADHD具有较好的治疗效果，其机制可能与调节脑肠肽分泌与肠道菌群结构有关。

Objective To explore the mechanism of action of Jingling Oral Liquid (JLOL) in the treatment of attention deficit hyperactivity disorder (ADHD), the effects of JLOL on the secretion of brain-gut peptides and the structure of intestinal flora in ADHD rats were observed. Methods Forty 3-week-old male SHR rats were randomly divided into a model group, a positive drug group (atomoxetine hydrochloride, 2.68 mg·kg^-1), and low-, medium-, and high-dose JLOL groups (2, 4, and 8 mL·kg^-1), with eight rats in each group. Eight male WKY rats of the same age were used as the control group. Each group of rats was ig administered the corresponding drug, while the control and model groups were ig administered deionized water, twice a day for 21 days. During the experiment, the changes in body weight of the rats were recorded; the behavioral changes of the rats were observed through the open field test and water maze test; the contents of gastrin (GAS), motilin (MTL), ghrelin (GHRL), vasoactive intestinal peptide (VIP), substance P (SP), and 5-hydroxytryptamine (5-HT) in the rat serum were detected by enzyme-linked immunosorbent assay (ELISA); and the structural changes of the intestinal flora in the rats were detected by metagenomics. Results Compared with the model group, the body weight of the JLOL group rats was significantly reduced (P<0.05); the total distance traveled and the time spent in the center area in the open field test were significantly reduced (P<0.05, 0.01), while the time spent at rest and in the peripheral area was significantly increased (P<0.05, 0.01, 0.001); the latency time in the water maze test was significantly shortened (P<0.05, 0.01, 0.001); the levels of GAS, MTL, SP, and GHRL in the serum were significantly increased (P<0.05, 0.001), while the levels of VIP and 5-HT were significantly decreased (P<0.05, 0.01); the species diversity of the intestinal flora was significantly improved, the abundance of Firmicutes was significantly increased, the abundance of Bacteroidota was significantly decreased, the relative abundance of Bacteroides, Bifidobacterium, Faecalibacterium, and Parabacteroides was upregulated, and the relative abundance of Clostridium, Enterobacter, and Ruminococcus was downregulated; the Chao1, Simpson, Observed, and Shannon indices all increased (P<0.05, 0.01, 0.001); Ruminococcus and Enterobacter were negatively correlated with the levels of GAS, MTL, GHRL, and SP in the serum, and positively correlated with the levels of VIP and 5-HT; Faecalibacterium, Parabacteroides, Bifidobacterium, and Bacteroides were positively correlated with the levels of GAS, MTL, GHRL, and SP in the serum, and negatively correlated with the levels of VIP and 5-HT. Conclusion JLOL has a good therapeutic effect on ADHD, and its mechanism may be related to the regulation of brain-gut peptide secretion and the structure of intestinal flora.

R965

国家自然科学基金资助项目（81874419）