ABSTRACT
Sepsis-induced myocardial dysfunction (SMD) is the major cause of death in sepsis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis contributes to the occurrence and development of SMD. Although Apelin confers direct protection against SMD, the potential mechanisms remain unclear. This study aimed to determine whether Apelin protects against SMD via regulation of NLRP3-mediated pyroptosis of cardiomyocytes. Experimental SMD was induced in wild-type (WT) control mice and Apelin knockout (Apelin-/-) mice by cecal ligation and puncture (CLP). Neonatal mouse cardiomyocytes (NMCs) were treated with lipopolysaccharide (LPS) to simulate the physiological environment of SMD in vitro. The expression of Apelin was greatly decreased in the plasma from septic patients and septic mouse heart. Knockout of Apelin aggravated SMD, evidenced by decreased cardiac function, and increased cardiac fibrosis and NLRP3 inflammasome and pyroptosis levels in CLP-treated Apelin-/- mice compared with WT mice. Overexpression of Apelin activated the AMPK pathway and thereby inhibited NLRP3 inflammasome-mediated pyroptosis of NMCs induced by LPS in vitro These protective effects were partially abrogated by AMPK inhibitor. In conclusion, Apelin attenuated SMD by inhibiting NLRP3-mediated pyroptosis via activation of the AMPK pathway. Apelin may serve as a promising therapeutic target for SMD.
ABSTRACT
OBJECTIVE: To identify the feasibility and safety of fossa infratemporalis approach for blind-needle at sphenopalatine ganglion so as to provide anatomical evidence for the operation and the prevention of non-immediate adverse reaction. METHODS: The variations of pterygopalatine fossae in sixty dry skulls were observed by selecting measuring points for facial skull width. The brains of six wet skulls were taken out,then acupuncture of fossa infratemporalis approach was applied. Sphenopalatine ganglion was separated accurately with the pterygopalatine segment of maxillary arteria retained in the pterygopalatine fossa after its paries posterior was opened. We detected whether the needle was inserted into pterygopalatine fossa. Measurements showed needle inserted depth, facial skull width,the distance between the needle and sphenopalatine ganglion,the distance between the needle and the pterygopalatine segment of maxillary arteria,the distance between the pterygopalatine segment of maxillary arteria and the crotaphitic nerve in pterygopalatine fossa. RESULTS: The distance between the slight hollow under bilateral arcus superciliaris was selected as skull width, and 3 dry skulls showed the variation of pterygopalatine fossa. Needles were inserted into the pterygopalatine fossae of the wet skulls (12 times). The proportion of the inserting depth to the distance between the slight hollow under bilateral arcus superciliaris was 44%-54%. Only twice did the needle contact sphenopalatine ganglion. The average distances between the sphenopalatine ganglion and the needle were (5.88±3.70) mm in the left side and (6.43±5.54) mm in the right side. The average distances between the needle and the pterygopalatine segment of maxillary arteria were (2.77±3.99) mm left and (2.53±3.10) mm right. The average distances between the pterygopalatine segment of maxillary arteria and the crotaphitic nerve in pterygopalatine fossa were (2.83±4.05) mm left and (2.67±4.95) mm right. The mean data between the two sides had no statistic significance about all the above indices (all P>0.05). CONCLUSIONS: Fossa infratemporalis approach is feasible for blind-needle at sphenopalatine ganglion with less possibility to contact it. The effect of treating nasitis may achieved by little distance to nerve. Pricking at the pterygopalatine segment of maxillary arteria may induce non-immediate adverse reaction. The safety and efficacy should be comprehensively considered. There is a proportional relationship between the width of the skull and the insertion depth of the needle. The inserting depth of 44 percent may appropriate accounted for skull width.
