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金丝桃苷调控nox4改善小鼠糖尿病肾病的实验研究
首发时间：2025-03-14
摘要：基于nox4氧化应激通路探究金丝桃苷（hyp）改善糖尿病肾病的作用及机制。将24只雄性 c57bl/6 小鼠随机分为正常组、模型组及金丝桃苷低剂量（10 mg/kg）和高剂量组（20 mg/kg）。采用高脂饲料喂养结合腹腔注射链脲佐菌素（stz）建立小鼠ⅱ型糖尿病模型。建模成功后，按设定剂量每日腹腔注射金丝桃苷，共持续8周。并于治疗结束后，检测小鼠的血糖浓度、糖化血清蛋白水平、血清肌酐及尿素氮等药效学指标；采用he和pas染色法观察肾脏组织的病理改变；免疫组织化学检测肾脏组织中α平滑肌肌动蛋白（α-sma）、纤连蛋白（fn）和nadph氧化酶4（nox4）的表达；分子对接模拟nox4分子与hyp的结合方式；实时荧光定量聚合酶链式反应（rt-qpcr）法检测肾脏组织中α-sma、fn和nox4的mrna表达水平。结果表明，与模型组比较，低和高剂量的金丝桃苷抑制高血糖导致的小鼠尿液量、尿蛋白和血清肌酐增加等肾功能异常，改善糖尿病肾病。组织病理学和免疫组化的结果表明，金丝桃苷低剂量和高剂量组逆转长期高血糖诱发的肾脏组织病理损伤，下调α-sma、fn等纤维化指标。除此之外，分子对接结果显示，hyp与nox4蛋白有较高的亲和力，并且rt-qpcr和免疫组化的结果表明，hyp可以逆转糖尿病导致的nox4基因和蛋白水平的升高。 综上所述，hyp通过靶向抑制nox4减少肾间质纤维化，改善肾功能，发挥对糖尿病小鼠肾脏的保护作用。?????
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experimental study on the regulation of nox4 by hyperforin to improve diabetic nephropathy in mice
abstract：to investigate the role and mechanism of hypericin (hyp) in ameliorating diabetic nephropathy based on nox4 oxidative stress pathway. twenty-four male c57bl/6 mice were randomly divided into normal group, model group, and hypericin low-dose (10 mg/kg) and high-dose group (20 mg/kg). the mouse type ii diabetes model was established by high-fat chow feeding combined with intraperitoneal injection of streptozotocin (stz). after successful modeling, the mice were injected intraperitoneally with hyp daily at a set dose for a total of 8 weeks. and at the end of the treatment, the pharmacodynamic indexes such as blood glucose concentration, glycosylated serum protein level, serum creatinine and urea nitrogen were detected in the mice; the pathological changes of renal tissues were observed by he and pas staining; immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-sma), fibronectin (fn), and nadph oxidase 4 (nox4) in renal tissues; and molecular docking was simulated binding mode of nox4 molecules with hyp; real-time fluorescence quantitative polymerase chain reaction (rt-qpcr) method was used to detect the mrna expression levels of α-sma, fn and nox4 in kidney tissues. the results showed that low and high doses of hyp inhibited abnormal renal functions such as increased urine volume, urinary protein and serum creatinine in mice caused by hyperglycemia, compared with the model group. the results of histopathology and immunohistochemistry showed that hyp at the low and high dose reversed the renal histopathological damages induced by long-term hyperglycemia, and down-regulated fibrosis indexes such as α-sma and fn. in addition to that, molecular docking results showed that hyp had a high affinity for nox4 protein, and the results of rt-qpcr and immunohistochemistry indicated that hyp could reverse the elevation of nox4 gene and protein levels caused by diabetes. in summary, hyp exerts protective effects on the kidney of diabetic mice by targeting nox4 inhibition to reduce renal interstitial fibrosis and improve renal function.?????
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金丝桃苷调控nox4改善小鼠糖尿病肾病的实验研究
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