升清降浊胶囊通过抑制NLRP3炎症小体激活改善糖尿病肾病的机制研究  

Mechanism of Shengqing Jiangzhuo Capsules in Improving Diabetic Nephropathy by Inhibiting the Activation of NLRP3 Inflammasome

作　　者：余燕娜[1] 董鑫 王亮亮 汤水福[1] YU Yanna;DONG Xin;WANG Liangliang;TANG Shuifu(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong Clinical Research Institute of Traditional Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东省中医临床研究院,广东广州510405

出　　处：《中药新药与临床药理》2025年第3期376-383,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家中医药传承创新中心科研专项重点项目(2022ZD09);广州市科技计划项目(2024A03J0134);国家自然科学基金青年科学基金项目(82305114)。

摘　　要：目的探讨升清降浊胶囊(SQJZC)改善糖尿病肾病(DN)的作用机制。方法C57/BL6小鼠通过腹腔注射链脲佐菌素建立DN模型;每周检测小鼠的血糖及体质量变化。升清降浊胶囊治疗8周后检测尿总蛋白(UTP)、血肌酐(Scr)、血尿素氮(BUN)水平。苏木素-伊红染色(HE)、过碘酸雪夫染色(PAS)检测肾脏结构变化。qPCR法及ELISA法检测肾脏及血清炎症因子变化。Western Blot法检测肾脏损伤相关标志物、NOD样受体含pyrin结构域3(NLRP3)炎症小体成分变化。结果升清降浊胶囊对小鼠血糖及体质量无明显影响。HE和PAS染色结果显示升清降浊胶囊治疗可改善肾小管空泡变性及坏死,减轻刷状缘脱落及纤维沉积。进一步研究结果表明,升清降浊胶囊治疗能够明显减轻糖尿病肾病小鼠UTP、Scr、BUN及血清炎症因子的水平(P<0.01)。Western Blot结果显示升清降浊胶囊干预减轻肾脏凋亡相关因子及肾损伤分子1(Kim-1)水平,抑制炎症小体成分NLRP3、凋亡相关斑点样蛋白(ASC)、半胱天冬酶1(Caspase-1)的表达(P<0.05,P<0.01)。结论升清降浊胶囊能够改善糖尿病肾病肾脏损伤,该种作用可能通过抑制NLRP3炎症小体实现。Objective To explore the mechanism of Shengqing Jiangzhuo Capsules(SQJZC)in improving diabetic nephropathy(DN).Methods DN model was established by intraperitoneal injection of streptozotocin in C57/BL6 mice.The changes of blood glucose and body mass of mice were detected every week.After 8 weeks of treatment,the levels of urine total protein(UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected.Hematoxylineosin staining(HHE)and Periodic Acid-Schiff staining(PAS)were used to detect the changes of renal structure.The changes of inflammatory factors in kidney and serum were detected by qPCR and ELISA.Western Blot was used to detect the changes of renal injury-related markers and NOD-like receptor pyrin domain-containing 3(NLRP3)inflammasome components.Results SQJZC had no significant effect on blood glucose and body mass of mice.HE and PAS staining results showed that SQJZC treatment improved renal tubular vacuolar degeneration and necrosis,reduced brush border shedding and fiber deposition.The results of further study showed that SQJZC treatment could significantly reduce the levels of UTP,Scr,BUN and serum inflammatory factors in diabetic nephropathy mice(P<0.01).Western Blot results showed that SQJZC intervention reduced renal apoptosis-related factors and kidney injury molecule 1(Kim-1)levels.The expressions of NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC)and cysteinyl aspartate specific proteinase-1(Caspase-1)were inhibited(P<0.05,P<0.01).Conclusion SQJZC can improve renal injury in diabetic nephropathy,which may be achieved by inhibiting NLRP3 inflammasome.

关 键 词：升清降浊胶囊 糖尿病肾病 NLRP3炎症小体 小鼠 

分 类 号：R285.5[医药卫生—中药学]