Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Biomed Pharmacother. 2021 Oct;142:112045. doi: 10.1016/j.biopha.2021.112045. Epub 2021 Aug 18.
Asthma is characterized by airway hyperresponsiveness(AHR), inflammation and remodeling. Autophagy and endoplasmic reticulum stress(ERS) are dysregulated in asthma, and ATG5 has attracted wide attentions a representative gene of autophagy. Previous evidence shows that acupuncture may treat asthma by regulating the immune environment.However,the precise mechanism involved in acupuncture's effects on asthma is unclear. Thus, we investigated the inner-relationships of acupuncture and ATG5-mediated autophagy, ERS and CD4 T lymphocyte differentiation in asthma.
Ovalbumin (OVA)-sensitized and challenged ATG5 and ATG5mice with asthma were treated by acupuncture at Dazhui(GV14),Feishu(BL13) and Zusanli(ST36),and sacrificed the next day.Then blood and bronchoalveolar lavage fluid (BALF)samples were collected to determine inflammatory cell counts and cytokine levels. Lung tissue samples were obtained for histological examination, and the spleen was harvested for flow cytometry.
Compared with the untreated group, acupuncture decreased BALF inflammatory cell counts and AHR in OVA-induced mice.Acupuncture decreased autophagy-related protein and mRNA (ATG5,Beclin-1,p62 and LC3B)amounts and ERS-related protein (p-PERK, p-IRE-1,Grp78, and ATF6)levels as well as autophagosome formation in lung tissue, concomitant with increased IFN-γ and decreased IL-4, IL-17 and TGF-β amounts in BALF.Consistently, the imbalance of CD4 T lymphocyte subsets(Th1/Th2 and Treg/Th17) was also corrected by acupuncture.Meanwhile, AHR and inflammation were decreased in ATG5 mice compared with ATGanimals,without affecting the therapeutic effect of acupuncture.
Acupuncture reduces airway inflammation and AHR in asthma by inhibiting ATG5-mediated autophagy to regulate endoplasmic reticulum stress and CD4T lymphocyte differentiation.
哮喘的特征为气道高反应性（AHR）、炎症和重塑。自噬和内质网应激（ERS）在哮喘中失调，ATG5 作为自噬的代表性基因引起了广泛关注。先前的证据表明，针刺可能通过调节免疫环境来治疗哮喘。然而，针刺治疗哮喘的确切机制尚不清楚。因此，我们研究了针刺与 ATG5 介导的自噬、ERS 和 CD4 T 淋巴细胞分化在哮喘中的内在关系。
卵清蛋白（OVA）致敏和激发哮喘的 ATG5 和 ATG5 敲除小鼠接受针刺治疗，针刺穴位为大椎（GV14）、肺俞（BL13）和足三里（ST36），次日处死。然后收集血液和支气管肺泡灌洗液（BALF）样本，以确定炎症细胞计数和细胞因子水平。获取肺组织样本进行组织学检查，并采集脾脏进行流式细胞术分析。
与未治疗组相比，针刺降低了 OVA 诱导的小鼠 BALF 炎症细胞计数和 AHR。针刺降低了肺组织中自噬相关蛋白和 mRNA（ATG5、Beclin-1、p62 和 LC3B）的含量以及 ERS 相关蛋白（p-PERK、p-IRE-1、Grp78 和 ATF6）的水平，并减少了自噬体的形成，同时增加了 BALF 中 IFN-γ 的含量，减少了 IL-4、IL-17 和 TGF-β 的含量。同样，针刺也纠正了 CD4 T 淋巴细胞亚群（Th1/Th2 和 Treg/Th17）的失衡。同时，与 ATG 小鼠相比，ATG5 敲除小鼠的 AHR 和炎症减轻，但不影响针刺的治疗效果。
针刺通过抑制 ATG5 介导的自噬来调节内质网应激和 CD4 T 淋巴细胞分化，减少哮喘中的气道炎症和 AHR。
