Role of microRNA-21 in sepsis-induced lung injury in rats: relationship with TRPM2 expression / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of microRNA-21 (miR-21) in sepsis-induced lung injury and the relationship with transient receptor potential melastatin 2 (TRPM2) expression in rats.Methods:Forty-eight clean-grade Wistar rats, half male and half female, weighing 250-300 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (SH group), sepsis group (S group), miR-21 inhibitor group (group MI), and miR-21 inhibitor plus TRPM2 blocker Gd3 + group.Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized rats.In MI group and MIG group, miR-21 inhibitor and miR-21 inhibitor plus TRPM2 blocker Gd3 + were injected through the tail vein, respectively, at 12 h before CLP.Carotid artery blood samples were collected at 24 h after CLP for blood gas analysis, PaO 2 was recorded, and oxygenation index was calculated.Animals were sacrificed, and lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio), expression of miR-21 and TRPM2 mRNA (quantitative real-time polymerase chain reaction), levels of malondialdehyde (MDA) and superoxide dismutase (SOD) (by spectrophotometer colorimetry) and levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) in serum (by enzyme-linked immunosorbent assay). Results:Compared with group SH, the oxygenation index and SOD activity were significantly decreased, and W/D ratio, lung injury score, MDA content, serum IL-6, IL-8 and TNF-α concentrations were increased in the other three groups, and the expression of miR-21 mRNA was up-regulated, and the expression of TRPM2 mRNA was down-regulated in group S ( P<0.05). Compared with group S, the oxygenation index, SOD activity and serum IL-6, IL-8 and TNF-α concentrations were significantly increased, and W/D ratio, lung injury score and MDA content were decreased in group MI, and the expression of miR-21 mRNA was down-regulated, and the expression of TRPM2 mRNA was up-regulated in MI and MIG groups ( P<0.05). Compared with group MI, the oxygenation index and SOD activity were significantly decreased, W/D ratio, lung injury score, MDA content, serum IL-6, IL-8 and TNF-α concentrations were increased, and the expression of TRPM2 mRNA was down-regulated in group MIG ( P<0.05). Conclusion:Up-regulated expression of miR-21 and down-regulated expression of TRPM2 are involved in the process of sepsis-induced lung injury in rats.