The Role Of Resolvin D1 On NLRP3 Inflammasome And NF-κB Signaling Pathway In STZ-induced Diabetic Retinopathy

Purpose To investigate the effect of resolvin D1(Rv D1)on the Nod-like receptor family pyrin domain-containing(NLRP3)inflammasome and nuclear factor-κB(NF-κB)pathway in streptozotocin(STZ)-induced diabetic retinopathy rats.Methods Rats were divided into four groups: control,STZ,Rv D1 and vehicle group.Rats with diabetic retinopathy induced by STZ in Rv D1 and vehicle groups were given intravitreal injection of Rv D1(1000 ng/kg)or the same dosage of vehicle,respectively.The BRB breakdown was determined using Evans blue.Hematoxylin-eosin staining was used to observe the pathological changes of retinal tissues.Real-time PCR were used to detect m RNA expressions of NLRP3,ASC,Casepase-1 in retina tissues.The location and expression of NLRP3 inflammasome components were detected using immunohistochemistry.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved caspase-1,phosphorylation ofNF-κB and IκBα.Retinal homogenate of rats were collected for the detection of the downstream molecules IL-1β and IL-18 of the NLRP3 inflammasome by ELISA kits.Results The permeability of the BRB in the STZ group was significantly increased 2.4-fold compared with controls.We observed disruption of retinal structures present in the retina resulting from an experimental model of diabetes,while improvements in the retina tissues were showed with treatment of Rv D1.Levels of NLRP3,ASC,cleaved caspase-1,IL-1β and IL-18 were all upregulated in the retinas of STZ-induced diabetic rats;however,these changes were partially inhibited by Rv D1 treatment.Furthermore,Rv D1 administration suppressed activation of NF-κB-related signaling pathway via inhibiting NF-κB phosphorylation and blockade of the degradation of IκBα,which was upregulated in STZ-induced diabetic retinopathy.Conclusions Rv D1 plays a protective role in STZ-induced diabetic retinopathy by inhibiting the level of activation of the NLRP3 inflammasome and NF-κB-related signaling pathway via inhibition of NF-κB phosphorylation and blockade of the degradation of IκBα,suggesting targeting of this pathway might be an effective strategy in treating diabetic retinopathy.