PTSD状态下HCN2-GLT-1在脊髓水平协同调控内脏高敏感性-中枢敏化的作用及机制研究

发布时间：2018-05-19 18:34

本文选题：应激障碍 + 创伤后　；参考：《解放军医学杂志》2014年10期

【摘要】：目的研究创伤后应激障碍(PTSD)状态下,超极化激活环核苷酸门控阳离子通道2(HCN2)与谷氨酸转运体-1(GLT-1)在脊髓水平协同调控内脏高敏感性-中枢敏化的作用及机制。方法成年雌性SD大鼠随机分为3组,即正常对照组(n=14)、PTSD内脏高敏感模型组(n=15)、PTSD+头孢曲松(CTX)组[给予CTX预处理,n=15)。采用连续单一应激(SPS)联合足底电击刺激法建立PTSD内脏高敏感大鼠模型。建模7d后,采用结直肠扩张(CRD)-内脏运动反射(VMR)评估各组内脏敏感性的改变;采用CTX选择性诱发编码GLT-1的基因转录,并采用激光共聚焦及免疫荧光技术研究脊髓HCN2的表达及CTX对其的影响。结果与正常对照组比较,PTSD组脊髓HCN2表达明显上调(78.05±6.49 vs121.12±4.85,P0.001);与PTSD组比较,PTSD+CTX组HCN2表达显著降低(121.12±4.85 vs 98.24±5.86,P=0.012);PTSD+CTX组HCN2表达比正常对照组明显升高(98.24±5.86 vs 78.05±6.49,P=0.024)。在20mmHg压力下行CRD时,PTSD组的AUCVMR明显高于PTSD+CTX组(0.2913±0.0229 vs 0.2175±0.0090,P=0.005);在40mmHg压力下行CRD时,PTSD组的AUCVMR明显高于正常对照组(0.6200±0.0278 vs 0.3786±0.0155,P0.001),亦高于PTSD+CTX组(0.6200±0.0278 vs 0.5038±0.0336,P=0.006);在60mmHg压力下行CRD时,与正常对照组比较,PTSD组AUCVMR明显增高(0.7663±0.0262 vs 0.5271±0.0212,P0.001),同时亦明显高于PTSD+CTX组(0.7663±0.0262 vs 0.6400±0.0245,P=0.001)。结论在PTSD内脏高敏感状态下,CTX可通过直接上调GLT-1表达并间接下调HCN2的表达协同发挥抗内脏伤害性刺激的作用,HCN2-GLT-1信号通路在脊髓水平协同参与了内脏高敏感性-中枢敏化调控作用,可能成为防止或抑制PTSD状态下内脏高敏感性-痛觉敏化新靶点之一。
[Abstract]:Objective to investigate the role and mechanism of hyperpolarization-activated cyclic nucleotide gated cationic channel 2hCN2) and glutamate transporter GLT-1 in the regulation of visceral hypersensitivity and central sensitization at spinal cord level in post-traumatic stress disorder (PTSD). Methods Adult female Sprague-Dawley rats were randomly divided into three groups: the normal control group (n = 14) and the control group (n = 15). PTSD visceral hypersensitivity rat model was established by continuous single stress (SPS) combined with plantar electric stimulation. After 7 days of modeling, the changes of visceral sensitivity in each group were evaluated by colorectal dilatation CRDD-visceral motor reflex (VMRR), and the gene transcription encoding GLT-1 was selectively induced by CTX. Laser confocal and immunofluorescence techniques were used to study the expression of HCN2 in spinal cord and the effect of CTX on it. Results compared with the normal control group, the expression of HCN2 in the spinal cord of the PTSD group was significantly up-regulated (78.05 卤6.49 卤4.85 vs121.12 卤4.85), and the expression of HCN2 in the CTX group was significantly lower than that in the PTSD group (121.12 卤4.85 vs 98.24 卤5.86 vs 78.05 卤6.49). The AUCVMR of PTSD group was significantly higher than that of PTSD CTX group (0.2913 卤0.0229 vs 0.2175 卤0.0090 P0. 005G) under 20mmHg pressure, and the AUCVMR of CRD group was significantly higher than that of normal control group (0. 6200 卤0.0278 vs 0.3786 卤0. 155g P0.001C), and higher than that of PTSD CTX group (0. 6200 卤0.0278 vs 0.5038 卤0. 336p 0.006). When 60mmHg pressure was under CRD, the AUCVMR of PTSD group was significantly higher than that of normal control group (0. 6200 卤0.0278 vs 0.3786 卤0. 155g P0.001g). Compared with the normal control group, the AUCVMR in the PTSD group was significantly higher than that in the PTSD CTX group (0.7663 卤0.0262 vs 0.5271 卤0.0212p 0.001g / L), and was significantly higher than that in the PTSD CTX group (0.7663 卤0.0262 vs 0.6400 卤0.0245Pu 0.001g / L). Conclusion under the condition of visceral hypersensitivity of PTSD, CTX may play a synergistic role in visceral nociceptive stimulation by directly up-regulating the expression of GLT-1 and indirectly down-regulating the expression of HCN2. HCN2-GLT-1 signaling pathway is involved in visceral hypersensitivity at spinal cord level. Armature sensitization regulation, It may be one of the new targets to prevent or suppress visceral hypersensitivity-pain sensitization in PTSD.
【作者单位】：第三军医大学大坪医院消化内科;第三军医大学大坪医院重庆野战外科研究所;
【基金】：国家自然科学基金(81070298/H0307) 重庆市重点基金(cstc2013jjB0143)~~
【分类号】：R749.5

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