P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult

IF 3 4区医学 Q2 NEUROSCIENCES

Purinergic Signalling Pub Date : 2024-04-27 DOI:10.1007/s11302-024-10009-y

Ting Zhang, Jing Lv, Zhong-yue Liu, Qiu-lian Lei, Ze-fei Jiang, Xiao-xiang Sun, Xing Yue, Xuan Li, Ke-li Zhu, Yun-kuan Yang, Ling Luo, Xin Cao

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Abstract

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson’s trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1β, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

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P2X7受体对ST36减轻β-肾上腺素能损伤时的心脏纤维化至关重要

P2X7受体（P2X7R）在炎症和纤维化过程中起着重要的调节作用，但祖传三针（ST36）是否能通过调节P2X7R抑制炎症和纤维化的研究还很有限。给野生型小鼠和 P2X7R 基因敲除小鼠皮下注射异丙肾上腺素 5 毫克/千克，连续 7 天；治疗组在 ST36 处接受电针刺激（EA），连续 7 个疗程。治疗 7 个疗程后，对小鼠进行马森氏三色染色以评估纤维化情况。通过形态学、心电图和超声心动图评估心脏功能和结构。为了描述 ST36 对炎症的影响，研究人员进行了 Western 印迹、苏木精和伊红染色、免疫组化、炎症细胞因子生化分析和透射电子显微镜检查。P2X7R 在 ISO 处理的小鼠中过表达。与 ISO 组的小鼠相比，ST36 点的 EA（而非非点的 EA）可减少 ISO 诱导的心脏纤维化、HW/BW 和 R+S 波的增加。此外，ST36 点的 EA 还能降低 ISO 在心室中上调的 P2X7R 和 NLRP3。此外，EA还降低了血清中的细胞因子IL-1β、IL-6和IL-18，抑制了泡沫细胞聚集、炎症细胞浸润和自噬。然而，ST36 EA 未能减轻 P2X7R 基因敲除小鼠的心脏纤维化和肥大。总之，ST36 位置的 EA 可通过 P2X7R 减轻 ISO 诱导的纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.