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雷公藤多苷调控HIF-1α/miR-155-5p/Nrf2通路改善大鼠肾病综合征的机制研究
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| 篇名： | 雷公藤多苷调控HIF-1α/miR-155-5p/Nrf2通路改善大鼠肾病综合征的机制研究 |
| TITLE： | Mechanistic study of Tripterygium wilfordii multiglucoside in improving nephrotic syndrome via regulating the HIF-1α/miR-155-5p/Nrf2 pathway |
| 摘要： | 目的 研究雷公藤多苷（TWM）对大鼠肾病综合征的改善作用机制。方法采用尾静脉注射阿霉素的方法复制肾病综合征模型大鼠。将造模成功的大鼠随机分为模型组（蒸馏水）、泼尼松组（10mg/kg）和TWM高、低剂量组（10、5mg/kg），另设置不造模的空白组（蒸馏水），每组9只。各组大鼠灌胃相应药液/蒸馏水，每天1次，连续6周。观察大鼠肾组织病理学形态；检测大鼠24h尿蛋白（24h-UTP）和血清中生化指标[白蛋白（ALB）、血尿素氮（BUN）、肌酐（SCr）、总胆固醇（CHOL）、甘油三酯（TG）]水平；检测大鼠肾组织中氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]水平；检测大鼠肾组织中缺氧诱导因子1α（HIF-1α）/微小RNA-155-5p（miR-155-5p）/核因子E2相关因子2（Nrf2）信号通路相关mRNA和蛋白表达水平。结果与空白组比较，模型组大鼠肾组织结构紊乱，肾小球少量坏死，肾小管上皮细胞水肿；24h-UTP，血清中SCr、BUN、CHOL、TG水平，肾组织中MDA水平，肾组织中HIF-1α、Kelch样ECH相关蛋白1（Keap1）mRNA和蛋白表达水平以及miR-155-5p表达水平均显著升高（P＜0.05）；血清中ALB水平、肾组织中SOD水平以及Nrf2mRNA和蛋白表达水平均显著降低（P＜0.05）。与模型组比较，TWM高、低剂量组大鼠肾损伤明显改善，上述定量指标水平均显著逆转（P＜0.05）。结论TWM可通过调控HIF-1α/miR-155-5p/Nrf2信号通路，减轻氧化应激损伤，从而改善大鼠肾病综合征。 |
| ABSTRACT： | OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway. |
| 期刊： | 2026年第37卷第05期 |
| 作者： | 陶伊璠；宋纯东；王旭；张冲；苏颖；郏溪栋；姜浩然 |
| AUTHORS： | TAO Yifan，SONG Chundong，WANG Xu，ZHANG Chong，SU Ying，JIA Xidong，JIANG Haoran |
| 关键字： | 雷公藤多苷；肾病综合征；氧化应激；HIF-1α/miR-155-5p/Nrf2信号通路 |
| KEYWORDS： | Tripterygium wilfordii multiglucoside； nephrotic syndrome； oxidative stress； HIF-1α/miR-155-5p/Nrf2 signaling |
| 阅读数： | 1 次 |
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