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雷公藤多苷对糖尿病肾病大鼠肾损伤的影响
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| 篇名： | 雷公藤多苷对糖尿病肾病大鼠肾损伤的影响 |
| TITLE： | Effects of Tripterygium wilfordii multiglycoside on renal injury in rats with diabetic nephropathy |
| 摘要： | 目的 基于肿瘤蛋白p53/微RNA-214（miR-214）/UNC-51样激酶1（ULK1）轴探讨雷公藤多苷（TWM）对糖尿病肾病（DN）大鼠肾损伤的影响。方法将雄性SD大鼠分为正常组（6只）和造模组（28只），造模组大鼠以高脂高糖饲料喂养+链脲佐菌素腹腔注射法建立DN模型。将造模成功的大鼠分为模型组、缬沙坦组[8.33mg/（kg·d）]、TWM组[6.25mg/（kg·d）]，每组8只。各组大鼠灌胃相应药液或生理盐水，每天1次，连续6周。末次给药后，检测各组大鼠尿液/血液中肝肾功能指标[24h尿蛋白定量（24h-UTP）、血尿素氮（BUN）、血肌酐（SCr）、白蛋白（ALB）、丙氨酸转氨酶（ALT）]、血脂指标（甘油三酯、总胆固醇）、血糖指标（空腹血糖）水平，观察其肾组织病理改变，并检测其肾组织中p53、ULK1、Beclin-1、微管相关蛋白1轻链3（LC3）蛋白及mRNA和miR-214的表达情况。结果与正常组比较，模型组大鼠肾小管上皮水肿明显，细胞肿胀，伴有淋巴细胞浸润；模型组和各药物组大鼠24h-UTP、BUN、SCr、ALT和糖脂指标水平，p53蛋白及mRNA和miR-214的表达均显著升高或上调，而ALB水平、LC3-Ⅱ/LC3-Ⅰ、LC3mRNA、ULK1、Beclin-1蛋白及mRNA的表达均显著降低或下调（P＜0.01）。与模型组比较，各药物组大鼠肾组织病理学损伤均有所好转；其24h-UTP、BUN、SCr、ALT和糖脂指标水平，p53蛋白及mRNA和miR-214的表达均显著降低或下调，而ALB水平、LC3-Ⅱ/LC3-Ⅰ、LC3mRNA、ULK1、Beclin-1蛋白及mRNA的表达均显著升高或上调（P＜0.01）。结论TWM能减轻DN大鼠的肾损伤，改善其肝肾功能和糖脂水平，上述作用可能与调控p53/miR-214/ULK1轴、恢复细胞自噬有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy. |
| 期刊： | 2025年第36卷第07期 |
| 作者： | 张冲；宋纯东；王墨；梁爽；郭笑笑；张晗寒；李培嘉；宋珂；陈晨晨 |
| AUTHORS： | ZHANG Chong，SONG Chundong， WANG Mo，LIANG Shuang，GUO Xiaoxiao，ZHANG Hanhan，LI Peijia，SONG Ke，CHEN Chenchen |
| 关键字： | 雷公藤多苷；糖尿病肾病；肾损伤；自噬；p53/miR-214/ULK1轴 |
| KEYWORDS： | Tripterygium wilfordii multiglycoside； diabetic nephropathy； renal injury； autophagy； p53/miR-214/ULK1 axis |
| 阅读数： | 6 次 |
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