[关键词]
[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。
[Key word]
[Abstract]
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.
[中图分类号]
R285.5
[基金项目]
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)