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  • The correlation analysis between the NLRP3 inflammasome and inflammatory reaction in venous ulcer of the lower extremity

    ObjectiveTo investigate the relationship between the nucleotide binding oligomerization domain like receptor protein 3 (NLRP3) inflammasome and inflammatory reaction of venous ulcer of lower extremity.MethodsTwenty-four patients with active venous ulcer of lower extremity (active ulcer group), 24 patients with non exudative venous ulcer of lower extremity as positive control (non-active ulcer group), and 24 patients with traumatic wound as negative control (traumatic-wound group) were enrolled. The clinical data of the three groups were compared, the tissue samples around the wound were harvested, and the expressions of NLRP3 protein were detected by immunohistochemistry among the three groups. Enzyme linked immunosorbent assay (ELISA) was used to detect the IL-1β and IL-18 protein levels, RT-PCR was used to detect the mRNA expressions of apoptosis associated speck like protein containing CARD (ASC), caspase-1, c-Jun N-terminal kinase (JNK), p38, nuclear factor (NF)-κB p65 and NF-κB inhibitor alpha (NF-κB IkBα), and Western blotting was performed to evaluate the level of NLRP3 inflammasome in wound tissues.ResultsThe inflammatory response in the non-active ulcer group and trauma-wound group were milder than that in the active ulcer group. The levels of IL-1β and IL-18 proteins in the active ulcer group were higher than those in the non-active ulcer group and the traumatic-wound group [IL-1β: (146.621±11.597) ng/L vs. (80.967±14.213) ng/L vs. (84.962±19.484) ng/L, F=136.200, P<0.001; IL-18: (119.814±12.788) ng/L vs. (72.899±17.220) ng/L vs. (48.131±10.407) ng/L, F=167.910, P<0.001]. The results of RT-PCR showed that the mRNA expressions of ASC [(0.030±0.012) ng/L vs. (0.021±0.005) ng/L vs. (0.016±0.004) ng/L, F=18.106, P<0.001], caspase-1 [(0.054±0.012) ng/L vs. (0.013±0.009) ng/L vs. (0.018±0.006) ng/L, F=130.372, P<0.001], NF-κB p65 [(0.093±0.015) ng/L vs. (0.038±0.013) ng/L vs. (0.043±0.014) ng/L, F=110.950, P<0.001], NF-κB IkB-α [(0.085±0.015) ng/L vs. (0.078±0.015) ng/L vs. (0.041±0.016) ng/L, F=53.070, P<0.001], and JNK [(0.075±0.018) ng/L vs. (0.042±0.013) ng/L vs. (0.039±0.014) ng/L, F=41.271, P<0.001] in the wound tissues of the active ulcer group were higher than those in the non-active ulcer group and the traumatic-wound group. And the mRNA expression of p38 in the wound tissues of the active ulcer group was lower than that in the non-active ulcer group [(0.050±0.008) ng/L vs. (0.064±0.014) ng/L, P<0.05]. The result of Western blotting showed that the relative expression level of NLRP3 protein in the wound tissues of the active ulcer group was higher than that in the trauma-wound group and non-active ulcer group (0.767±0.272 vs. 0.605±0.212 vs. 0.556±0.183, F=4.804, P=0.012).ConclusionNLRP3 inflammasome is closely related to the wound in venous ulcer of lower extremity and provides a new target to the therapy of venous ulcer of lower extremity.

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