Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor.

Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor.
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没食子酸通过抑制 P2X7 受体减轻内脏疼痛和抑郁。

DOI:
10.3390/ijms23116159
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发表时间:
2022-05-31
影响因子:
5.6
通讯作者:
Gao, Yun
Gao, Yun
中科院分区:
生物学2区
文献类型:
--
作者:
Wen, Lequan;Tang, Lirui;Zhang, Mingming;Wang, Congrui;Li, Shujuan;Wen, Yuqing;Tu, Hongcheng;Tian, Haokun;Wei, Jingyi;Liang, Peiwen;Yang, Changsen;Li, Guodong;Gao, Yun

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慢性内脏疼痛可能发生在许多疾病中,其中最常见的是肠易激综合征(IBS)。此外,抑郁症是慢性内脏疼痛的常见合并症。 P2X7 受体在炎症过程中至关重要,并且与疼痛和抑郁的发生密切相关。没食子酸是一种可以从中药中提取的酚酸,已被证明具有抗炎和抗抑郁作用。在这项研究中,我们研究了没食子酸是否可以通过降低 P2X7 受体的表达来缓解共病内脏疼痛和抑郁。为此,使用腹部撤回反射评分来测量患有内脏疼痛和抑郁的大鼠的疼痛阈值,而使用蔗糖偏好测试、强迫游泳测试和旷场测试来量化每只大鼠的抑郁水平。通过蛋白质印迹和实时定量 PCR 评估海马、脊髓和背根神经节 (DRG) 中 P2X7 受体的表达。此外,通过免疫荧光实验研究了海马和背根神经节中P2X7受体和胶质纤维酸性蛋白(GFAP)的分布。使用蛋白质印迹法测定p-ERK1/2和ERK1/2的表达。采用酶联免疫吸附法测定血清中IL-1β、TNF-α、IL-10的浓度。我们的结果表明,没食子酸能够减轻所研究的大鼠的疼痛和抑郁。没食子酸还降低了这些大鼠海马、脊髓和背根神经节中 P2X7 受体和 p-ERK1/2 的表达。此外,没食子酸治疗降低了这些大鼠的血清 IL-1β 和 TNF-α 浓度,同时提高了 IL-10 水平。因此,没食子酸可能是通过抑制海马、脊髓和背根神经节中 P2X7 受体的表达来治疗内脏疼痛和抑郁共病的有效新候选药物。
Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1β, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1β and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.
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