棕矢车菊素调节SIRT1/FoxO3信号通路对糖尿病肾病大鼠炎症反应的影响
Jaceosidin regulates the inflammatory response in rats with diabetic nephropathy by the SIRT1/FoxO3 signaling pathway
王亮 1刘安宁 1陈利灵 1郑宽勇 1李红玲1
作者信息
- 1. 长江大学附属仙桃市第一人民医院 内分泌科,仙桃 433000
- 折叠
摘要
为探讨棕矢车菊素对糖尿病肾病(diabetic nephropathy,DN)大鼠炎症反应的影响,将SD雄性大鼠随机分为对照组、模型组、棕矢车菊素低(10 mg/kg)剂量组、棕矢车菊素高(20 mg/kg)剂量组、阳性对照组(500 mg/kg二甲双胍)、抑制剂组[20 mg/kg 棕矢车菊素+5 mg/kg 沉默信息调节因子 2 相关酶 1(silent mating-type information regulation 2 homolog 1,SIRT1)抑制剂 EX-527],每组12只.除对照组外,其他组大鼠均采用高脂饲料喂养联合化学诱导法构建DN大鼠模型,模型构建成功后,每天药物灌胃1次,持续4周.采用酶标仪检测末次给药后大鼠肾功能变化;ELISA检测大鼠血清炎性因子表达水平;H-E染色观察大鼠肾脏组织病变;免疫组化法检测大鼠肾脏组织足细胞裂孔膜蛋白Nephrin和膜蛋白Podocin表达;Western blotting检测大鼠肾脏组织中SIRT1/叉头状转录因子O3(forkhead box protein O3,FoxO3)信号通路相关蛋白表达.结果显示,与对照组比较,模型组大鼠肾脏组织间质炎性浸润明显,肾小球肥大,肾小管细胞空泡变性,肾功能减弱,血清炎性因子、FoxO3表达显著升高,Nephrin、Podocin、磷酸化 SIRT1(phosphorylated SIRT1,p-SIRT1)/SIRT1 表达水平显著降低(P＜0.05);与模型组比较,棕矢车菊素低、高剂量组和阳性对照组大鼠肾脏病变明显改善,肾功能增强,血清炎性因子、FoxO3表达显著降低,Nephrin、Podocin、p-SIRT1/SIRT1表达水平显著升高(P＜0.05);加入SIRT1抑制剂EX-527后,减弱了棕矢车菊素对DN大鼠炎症反应的抑制作用.该研究提示,棕矢车菊素可通过调节SIRT1/FoxO3信号通路缓解DN大鼠体内的炎症反应.
Abstract
This study aims to investigate the influence of jaceosidin on inflammatory response in diabetic nephropathy(DN)rats.Male SD rats were randomly divided into control group,model group,low(10 mg/kg)and high(20 mg/kg)dose jaceosidin groups,positive control group(500 mg/kg metformin),and inhibitor group(20 mg/kg jaceosidin+5 mg/kg silent mating-type information regulation 2 homolog 1[SIRT1]inhibitor EX-527),with 12 animals in each group.Except for the control group,all rats were fed with high-fat diet combined with chemical induction to establish the rat DN model.After the model was successfully established,animals were treated with drugs by gavage,once a day for four weeks.Kidney function changes were detected by microplate reader and the expressions of inflammatory factors were detected by ELISA.The pathological changes of the kidney were examined by H-E staining and the expressions of nephrin and podocin in renal tissues were detected by immunohistochemistry.The expressions of SIRT1/forkhead box protein O3(FoxO3)signaling pathway-related proteins in renal tissues were detected by Western blotting.The results showed that compared to the control group,the model group showed obvious interstitial inflammatory infiltration,glomerular hypertrophy,and vacuolar degeneration of renal tubular cells,impaired kidney functions,serum inflammatory factors and FoxO3 expression were significantly increased,while the nephrin,podocin,and phosphorylated SIRT1(p-SIRT1)/SIRT1 expression levels were significantly decreased(P＜0.05).Compared to that of the model group,the pathological injury of the renal tissues in the low-dose and high-dose jaceosidin groups and the positive control group was significantly improved,and kidney functions were restored,while serum inflammatory factors and FoxO3 expression were significantly decreased,while the expressions of nephrin,podocin,and p-SIRT1/SIRT1 were significantly increased(P＜0.05).Adding SIRT1 inhibitor EX-527 attenuated the anti-inflammatory effect of jaceosidin.The study suggests that jaceosidin can alleviate inflammatory response in DN rats by regulating the SIRT1/FoxO3 signaling pathway.
关键词
糖尿病肾病/棕矢车菊素/沉默信息调节因子2相关酶1/叉头状转录因子O3/炎症反应Key words
diabetic nephropathy/jaceosidin/silent mating-type information regulation 2 homolog 1/forkhead box protein O3/inflammatory response引用本文复制引用
基金项目
2022年度仙桃市第一人民医院院级科研项目(XXY2022002)
出版年
2024
NETL
NSTL
万方数据