Electroacupuncture attenuates acute lung injury induced by sepsis via NLRP3/caspase-1 pathway mediated pyrocytosis pathway
ZHANG Hao,SU Qian,SHI Jia
Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin300100,China
Abstract:
Objective To observe whether electroacupuncture at Zusanli (ST36) and Feishu (BL13) acupoints reduces sepsis induced acute lung injury in rats through the pyroptosis pathway mediated by NLRP3/caspase-1 pathway. Methods Thirty adult healthy male SD rats were randomly divided into five groups: control group, model group, electroacupuncture group, electroacupuncture plus NLRP3 activator group, and non-acupoint electroacupuncture group, with six rats in each group. The sepsis model was established by cecal ligation and puncture. In the electroacupuncture group, bilateral ST36 and BL13 acupoints were stimulated with dense and sparse wave electroacupuncture (once daily for 5 days before model preparation, once every 6 hours during model preparation, 30 minutes each time). In the non-acupoint electroacupuncture group, the same parameters of electroacupuncture were applied at non-acupoints located 5mm away from ST36 and BL13. The electroacupuncture plus NLRP3 activator group received intraperitoneal injection of 100mg/kg nigericin sodium salt 30 minutes before model preparation. After modeling, the rats were sacrificed at 24 hours, and lung tissues were collected to calculate the wet-to-dry weight ratio (W/D ratio), observe pathological changes, and evaluate lung injury scores. The levels of IL-1β, IL-18 in lung tissues were measured by ELISA, and the expression levels of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were detected by Western blot. Results Compared with the control group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the model group, electroacupuncture group, electroacupuncture plus NLRP3 activator group, and non-acupoint electroacupuncture group were increased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were upregulated, and the differences were statistically significant (P<0.05). Compared with the model group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the electroacupuncture group were decreased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were downregulated, and the differences were statistically significant (P<0.05). Compared with the electroacupuncture group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the electroacupuncture plus NLRP3 activator group were increased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were upregulated, and the differences were statistically significant (P<0.05). Conclusion Electroacupuncture stimulation at ST36 and BL13 acupoints may alleviate acute lung injury in rats with sepsis through inhibiting the classical cell pyroptosis pathway mediated by NLRP3/caspase-1 pathway.