【目的】探究大蒜素对2 型糖尿病肾病（DN）的治疗作用及机制。【方法】将27 只雄性SD 大鼠随机分为假手术组、模型组 与大蒜素组，每组9 只。模型组与大蒜素组大鼠构建DN 模型。建模成功后，分组灌胃干预。检测肾功能指标、氧化应激指 标，采用荧光探针法检测大鼠肾组织中活性氧（ROS）水平，通过碘酸-希夫（PAS）染色、苏木精-伊红（HE）染色观察肾组织 病理形态，采用透射电镜观察肾组织细胞超微结构，Western Blot 法观察肾组织焦亡相关蛋白[气体衍生蛋白E（GSDME）、 NLR 家族pyrin 结构域蛋白1（NLRP1）、NLR 家族pyrin 结构域蛋白3（NLRP3）、半胱氨酸天冬氨酸特异性蛋白酶1（Caspase1）、 热休克蛋白家族A 成员1B（HSPA1B）]水平，实时定量逆转录聚合酶链式反应（RT-qPCR）法检测肾组织细胞色素P450 家族1 亚家族B 成员1 反义RNA1（CYP1B 1-AS1）mRNA 表达水平，RNA 免疫共沉淀（RIP）法验证HSPA1B 与CYP1B 1-AS1 互作情 况。【结果】与假手术组比较，模型组肾功能指标、氧化应激水平明显异常，肾组织炎症浸润、糖原沉积及细胞出现焦亡特 征，肾组织ROS 水平升高，焦亡相关蛋白（GSDME、NLRP1、NLRP3、Caspase1、HSPA1B）及CYP1B 1-AS1 mRNA 表达水平 升高（P＜0.05）；与模型组比较，治疗组大鼠肾功能指标、氧化应激水平显著改善，肾组织炎症浸润、糖原沉积及细胞焦亡 特征减轻，肾组织ROS 水平降低，焦亡相关蛋白（GSDME、NLRP1、NLRP3、HSPA1B、Caspase1）及CYP1B 1-AS1 mRNA 表 达水平下调（P＜0.05）。RIP 实验证实HSPA1B 与CYP1B 1-AS1 存在互作。【结论】大蒜素可通过调控CYP1B 1-AS1/HSPA1B/ ROS 通路，减轻肾组织氧化应激损伤与细胞焦亡，进而缓解DN 进展。

Objective To investigate the therapeutic effects and underlying mechanism of allicin on type 2 diabetic nephropathy（DN）. Methods Twenty-seven male SD rats were randomly divided into a sham-operated group，a model group，and an allicin group，with 9 rats in each group. The DN model was established in rats from the model and allicin groups. After successful modeling，the groups received respective interventions. Renal function indicators and oxidative stress markers were assessed. Reactive oxygen species（ROS）level in rat kidney tissues was detected using a fluorescent probe method. Renal histopathology was observed by periodic acid-Schiff（PAS） staining and hematoxylin-eosin（HE）staining，and the ultrastructure of renal tissue cells was examined by transmission electron microscopy. Western Blot analysis was employed to detect pyroptosis-related proteins [gasdermin E（GSDME），NLR family pyrin domain containing 1（NLRP1），NLR family pyrin domain containing 3 （NLRP3），caspase-1，and heat shock protein family A member 1B（HSPA1B）] in renal tissues. Quantitative real-time reverse transcription polymerase chain reaction（qRT-PCR）was used to measure the mRNA expression level of cytochrome P450 family 1 subfamily B member 1 antisense RNA 1（CYP1B 1-AS1）. RNA immunoprecipitation （RIP）assay was performed to validate the interaction between HSPA1B and CYP1B 1-AS1. Results Compared with the sham-operated group，the model group exhibited significantly abnormal renal function indicators and oxidative stress levels，marked inflammatory infiltration，glycogen deposition，and characteristic features of pyroptosis in renal tissues. ROS level in renal tissues was significantly elevated，accompanied by increased protein expression levels of pyroptosis-related markers（GSDME，NLRP1，NLRP3，Caspase1，HSPA1B）and upregulation of CYP1B 1-AS1 mRNA expression（P＜0.05）. In contrast，compared with the model group，the allicin-treated group demonstrated significantly improved renal function and oxidative stress parameters，alleviated renal inflammatory infiltration，glycogen deposition，and pyroptotic features. ROS level in renal tissues was notably reduced，and the expression levels of pyroptosis-related proteins（GSDME，NLRP1，NLRP3，HSPA1B， Caspase1）and CYP1B 1-AS1 mRNA were significantly downregulated（P＜0.05）. RIP assay confirmed the interaction between HSPA1B and CYP1B 1-AS1. Conclusion Allicin can mitigate the progression of DN by regulating the CYP1B 1-AS1/HSPA1B/ROS pathway，and alleviating oxidative stress damage and pyroptosis in renal tissues.

R285.5

福建省自然科学基金项目（编号：2023J011898、2024J011612）；龙岩市科技计划项目（编号：2024LYF 17034）；福建医科大学 启航基因项目（编号：2022QH1340）