姜黄素对视网膜缺血.再灌注损伤大鼠视网膜ＩＬ.１β表达的影

Objective To observe the effect of curcumin (CUR) on retinal interleukin-1β (IL-1β) of retinal ischemia-reperfusion injury (RIRI) rats and its mechanism from the toll-like receptor 4/cysteine-containing aspartate-specific proteases-8 (TLR4/Caspase-8) signaling pathway, providing a scientific theoretical basis for the clinical application of CUR in the treatment of RIRI. Methods　Totally 102 specific-pathogen-free healthy male Sprague Dawley rats without eye disease were included and randomly divided into the Sham group (n=10), RIRI group (n=35), RIRI+TLR4 inhibitor (TAK-242) group (n=11), RIRI+CUR group (n=35) and RIRI+CUR+TAK-242 group (n=11). Rats in the Sham Group, RIRI group and the RIRI+CUR group were further divided into subgroups according to the different time points after modeling: 6 h, 12 h, 24 h, 72 h and 7 d. The RIRI model was established by the anterior chamber ocular hypertension method in the RIRI group. Rats in the Sham group did not receive special treatment. Rats in the RIRI+TAK-242 group, the RIRI+CUR group and the RIRI+CUR+TAK-242 group were injected with corresponding drugs before modeling. The cell numbers of IL-1β+, TLR4+ and Caspase-8+ in the retinas of rats in each group at each time point after modeling were detected through immunohistochemical staining. The expression of TLR4, Caspase-8 and IL-1β in the retinas of rats in each group was detected via Western blot 12 h after modeling. The morphological changes of the retina of rats in each group were observed by hematoxylin-eosin staining. Results The results of immunohistochemical staining showed that at 6 h, 12 h, 24 h, 72 h and 7 d after modeling, the cell number of IL-1β+ and TLR4+ significantly increased in the RIRI+CUR group compared with the Sham group. The cell number of IL-1β+ and TLR4+ significantly decreased in the RIRI+CUR group at each time point compared with the RIRI group. The cell number of IL-1β+ and TLR4+ significantly increased in the RIRI group at each time point compared with the Sham group. The above differences were statistically significant (all P<0.05). At 12 h after modeling, compared with the Sham group, the cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly increased in the RIRI group, RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group. The cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly decreased in the RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group compared with the RIRI group. The cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly increased in the RIRI+TAK-242 group and RIRI+CUR group compared with the RIRI+CUR+TAK-242 group. The above differences were statistically significant (all P<0.05). At 12 h after modeling, there was no statistically significant difference between the RIRI+TAK-242 group and the RIRI+CUR group in terms of the cell number of IL-1β+, TLR4+ and Caspase-8+ as well as the proteins IL-1β, TLR4 and Caspase-8 (all P>0.05). At 12 h after modeling, compared with the Sham group, the retinal inner layer cells in rats were edematous, the inner retinal layer was thickened, and the number of retinal ganglion cells (RGCs) was significantly reduced in the RIRI group, RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group. Conclusion CUR can down-regulate the expression of IL-1β in the retina of RIRI rats, thereby reducing RIRI in rats. This mechanism may be related to the regulation of the TLR4/Caspase-8 signaling pathway by CUR, which has a neuroprotective effect.