Liu Q F, Li L, Guo Y Q, Li X, Mou Z D, Wang X, Du G Z
Department of Pathogenic Biology, Chengdu Medical College, Chengdu 610083, China - Email:
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China - Email:
Arch Ital Biol. 2016 Dec 1;154(4):133-142. doi: 10.12871/00039829201644.
We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed. 'Wet-dog' shakes, teeth chattering, and the total scores of withdrawal reactions were reduced. TLR4 expression and Glu levels were reduced, whereas GAD67 and GABA levels were increased. Overall, these findings indicate that modifying TLR4 gene expression in the vlPAG stimulates expression of the downstream signaling molecule, GAD67, which decreases Glu levels and increases GABA levels. This mechanism may explain the inhibition of withdrawal syndrome in morphine-dependent rats.
我们评估了Toll样受体4（TLR4）基因在吗啡依赖大鼠腹外侧导水管周围灰质（vlPAG）区域对减轻戒断综合征以及调节谷氨酸脱羧酶（GAD67）、谷氨酸（Glu）和γ-氨基丁酸（GABA）的作用。在通过小干扰RNA（siRNA）介导下调TLR4后，观察到戒断行为和下游信号分子的变化。将TLR4 siRNA注射到大鼠的vlPAG中，随后连续5天腹腔注射吗啡，然后注射纳洛酮，并观察吗啡戒断的行为指标。“湿狗”样抖动、牙齿打颤和戒断反应的总分均降低。TLR4表达和Glu水平降低，而GAD67和GABA水平升高。总体而言，这些发现表明，改变vlPAG中的TLR4基因表达会刺激下游信号分子GAD67的表达，从而降低Glu水平并增加GABA水平。这一机制可能解释了对吗啡依赖大鼠戒断综合征的抑制作用。
