目的：研究焦亡在糖尿病视网膜病变(DR)发生过程中的作用机制，探索介导DR的环状RNA(circRNA)及其靶向微小RNA(miRNA)调控焦亡的机制，为防治DR提供新靶点、新思路。

方法：建立STZ诱导的SD大鼠1型糖尿病模型。检测糖尿病大鼠视网膜组织中circRNA_0076631、miR-214和焦亡相关因子的表达情况。应用CCK-8、小管样结构形成实验测定不同浓度葡萄糖对人视网膜微血管内皮细胞(HRMECs)的增殖能力及成管能力的影响。通过qRT-PCR、Westernblot检测circRNA_0076631、miR-214和焦亡相关因子(NLRP3、caspase-1和IL-1β)在HRMECs中的表达，并检测干扰circRNA_0076631后焦亡信号通路因子的表达情况。采用共转染circRNA_0076631抑制剂(ASO-circRNA_0076631)、miR-214过表达转染试剂和miR-214抑制剂(AMO-miR-214)实验进一步明确circRNA_0076631、miR-214、caspase-1三者的作用关系，阐明该通路在DR中的作用机制。

结果：circRNA_0076631及焦亡信号通路因子(NLRP3、caspase-1和IL-1β)mRNA在糖尿病组视网膜及25 mmol/L葡萄糖干预24 h的HRMECs中异常高表达，而miR-214 mRNA表达降低(均P<0.05)。过表达miR-214后焦亡核心因子caspase-1 mRNA表达降低，抑制miR-214后caspase-1 mRNA表达上调(均P<0.05)。干扰circRNA_0076631后HRMECs中caspase-1 mRNA表达下调(P<0.05)。联合转染实验发现干扰circRNA_0076631后caspase-1 mRNA表达被抑制(均P<0.05)，但在共转染miR-214抑制剂后caspase-1 mRNA表达增加(均P<0.05)。

结论：circRNA_0076631和焦亡均参与DR的发生，circRNA_0076631可能通过调节miR-214介导焦亡信号通路因子caspase-1表达，从而参与DR的焦亡信号通路，进而影响DR的发生，而circRNA_0076631有望作为一种新的治疗靶点，为防控DR提供新思路。

METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.

RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).

CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.