Effect of Electroacupuncture Preconditioning on Activation of NEK7-NLRP3 Inflammasome in Lung Tissue of Rats with Sepsis Acute Lung Injury

  OBJECTIVE  To observe the effect of electroacupuncture (EA) pretreatment at "Zusanli" (ST 36) and "Chize" (LU 5) points on the activation of NEK7-NLRP3 inflammasome in the lung tissue of rats with sepsis acute lung injury (ALI), and to explore the protective effect and possible mechanism of EA pretreatment in septic ALI.

  METHODS  According to the principle of randomization, 40 rats were equally divided into 4 groups, namely the control group, EA preconditioning+control group, model group and EA preconditioning+model group. The septic ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS). EA (4 Hz/20 Hz, 1-2 mA) was applied to bilateral ST 36 and LU 5 for 30 min, once a day for 7 consecutive days before modeling. The lung function of the rats was detected; HE staining was used to observe the pathological changes of the lung, and the degree of pulmonary edema in the left lung of rats was detected by the ratio of wet/dry weight of the lung; the secretions of inflammatory factors IL-1β and IL-18 in the plasma and lung tissue were measured by ELISA kits; the positive expression of ASC protein in the lung tissue of rats was observed by immunofluorescent staining; the expression of NEK7, NLRP3, Caspase-1 and IL-1β protein was assayed by Western blot.

  RESULTS  Compared with the control group, the forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV_0.1), FEV_0.3, FEV_0.1/FVC, FEV_0.3/FVC were significantly decreased (P < 0.001); Inflammatory cell infiltration in the lung tissue was obvious and accompanied by congestion and edema, and the alveolar structure was ruptured; the ratio of W/D was significantly increased (P < 0.001); the contents of IL-1β and IL-18 in plasma and lung tissue were significantly increased (P < 0.001) while the ASC protein positive expression was increased significantly (P < 0.001); the expression levels of inflammasome-related proteins NEK7, NLRP3, Caspase-1 and IL-1β in lung tissue were significantly increased in the model group (P < 0.001). After EA intervention, the FVC, FEV_0.1, FEV_0.3, FEV_0.1/FVC, FEV_0.3/FVC were significantly increased (P < 0.05, P < 0.001), and the lung pathology has improved significantly. The other indicators mentioned above were significantly decreased in the EA preconditioning+model group (P < 0.05, P < 0.01, P < 0.001).

  CONCLUSION  EA pretreatment can reduce pulmonary inflammatory response and improve lung function in septic ALI rats, which is relevant with inhibiting the activation of NEK7-NLRP3 inflammasome.