| 臧春雪,高天舒,张凤暖,赖倚文.基于管球反馈机制探讨渴络欣胶囊对糖尿病肾病大鼠早期高滤过的影响[J].,2023,43(7):822-830 |
| 基于管球反馈机制探讨渴络欣胶囊对糖尿病肾病大鼠早期高滤过的影响 |
| Effect of Keluoxin Capsule on Early Hyperfiltration in Diabetic Kidney Disease Rats Based on Tubuloglomerular Feedback Mechanism |
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| DOI：10. 7661/j. cjim. 20230407.070 |
| 中文关键词: 糖尿病肾病 渴络欣胶囊 早期高滤过 管球反馈 中药 |
| 英文关键词:diabetic kidney disease Keluoxin Capsule early hyperfiltration tubuloglomerular feedback Chinese herbal medicine |
| 基金项目:北京医卫健康公益基金会资助项目（No.YWJKJJHKYJJ-KH2019004）;沈阳市临床医学研究中心（No.沈科发[2018]75号-5） |
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| 中文摘要: |
| 目的 探讨渴络欣胶囊对糖尿病肾病大鼠疗效及是否通过管球反馈机制发挥作用。方法 自100只雄性SD大鼠中随机取25只作为正常组，余75只采用高脂高糖饮食联合小剂量链脲佐菌素腹腔注射建立糖尿病大鼠模型，将成模大鼠随机均分为模型组、渴络欣组和氯沙坦组，每组25只。渴络欣组予渴络欣胶囊每日5.4 g/kg灌胃，氯沙坦组予氯沙坦片每日9 mg/kg灌胃，正常组和模型组予等体积蒸馏水灌胃，持续11周。每2周测1次随机血糖。第6、11周结束后取材。采用酶联免疫吸附测定法检测24 h尿微量白蛋白、肾小管损伤相关蛋白和尿素氮、血尿肌酐;行苏木素-伊红染色、糖原染色、马松染色观察大鼠肾脏病理变化;免疫组化法观察大鼠肾钠-葡萄糖共转运蛋白1（SGLT1），钠-葡萄糖共转运蛋白2（SGLT2）、钠-钾-氯协同转运蛋白2（NKCC2）表达，免疫荧光观察腺苷1型受体（A1AR）在肾脏定位;蛋白免疫印迹法和实时荧光定量聚合酶链式反应检测肾组织SGLT1、SGLT2、NKCC2、A1AR的表达。结果 与正常组比较，模型组大鼠基底膜增厚，肾小管上皮细胞脱落，渴络欣组较模型组改善。与正常组比较，模型组大鼠随机血糖、24 h尿微量白蛋白、肾小管损伤相关蛋白、肾脏指数和内生肌酐清除率均升高（P<0.05）。与模型组比较，渴络欣、氯沙坦组上述指标均好转（P<0.05）。与正常组比较，6、11周时模型组SGLT1，SGLT2蛋白及mRNA表达均升高（P<0.05），与模型组比较，渴络欣组SGLT1，SGLT2蛋白及mRNA表达下降（P<0.01）。与正常组比较，模型组6周时NKCC2蛋白表达升高（P<0.01），11周时A1AR蛋白表达下降（P<0.01）。与模型组比较，11周时渴络欣组及氯沙坦组NKCC2蛋白及mRNA表达升高（P<0.01），A1AR蛋白表达升高（P<0.01）。结论 渴络欣具有改善DKD大鼠肾小球和肾小管损伤，减轻早期肾脏高滤过的作用，其机制可能与调节管球反馈有关。 |
| 英文摘要: |
| Objective To investigate the therapeutic effect of Keluoxin Capsule on diabetic kidney disease（DKD）in rats and explore whether it exerts its effects through the tubuloglomerular feedback mechanism.Methods Out of 100 male SD rats，25 rats were randomly selected as the normal group，while the remaining 75 rats were fed a high-fat and high-sugar diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish diabetic rat model.The rat models were randomly and equally divided into model group，Keluoxin group and losartan group，25 rats in each group.The rats in the Keluoxin group were treated with Keluoxin Capsules （5.4 g·kg-1·d-1） by gavage，those in the losartan group were treated with losartan tablets （9 mg·kg-1·d-1） by gavage，and those in the normal group and the model group were both treated with an equivalent volume of distilled water by gavage for 11 weeks.Random blood glucose was measured every 2 weeks.Samples were collected at the end of weeks 6 and 11.Enzyme-linked immunosorbent assay was used to measure 24-hour urinary microalbumin，renal tubular injury-related proteins，blood urea nitrogen，blood and urine creatinine.Hematoxylin-eosin staining，glycogen staining，and Masson staining were performed to observe the pathological changes in the rat kidneys.Immunohistochemistry was utilized to assess the expression of sodium-glucose cotransporter 1 （SGLT1），sodium-glucose cotransporter 2 （SGLT2），and sodium-potassium-chloride cotransporter 2 （NKCC2） in the rat kidneys.Additionally， immunofluorescence was utilized to observe the localization of A1 adenosine receptor （A1AR） in the rat kidneys.The expressions of SGLT1，SGLT2，NKCC2 and A1AR in rat kidney tissue were detected by Western Blot and Real-time fluorescent quantitative polymerase chain reaction.Results Compared with the normal group，the model group rats had thickened basement membranes and detached renal tubular epithelial cells，which were improved in the Keluoxin group compared with the model group.Compared with the normal group，the model group rats had increased random blood glucose，24-hour urinary microalbumin，renal tubular injury-related proteins，kidney index，and endogenous creatinine clearance rate （P<0.05）.Compared with the model group，the above indicators were improved in the Keluoxin and losartan groups （P<0.05）.Compared with the normal group，the expression of SGLT1 and SGLT2 proteins and mRNA in the model group rats was increased at 6th and 11th week （P<0.05）， which was significantly decreased in the Keluoxin group compared with the model group（P<0.01）.Compared with the normal group，the NKCC2 protein in the model group rats was increased at the 6th week （P<0.01），and the A1AR protein was down-regulated at the 11th week （P<0.01）.Compared with the model group，the NKCC2 protein and mRNA were significantly increased in the Keluoxin group and losartan group at the 11th week （P<0.01），and A1AR protein was significantly increased （P<0.01）.Conclusion Keluoxin has the effect of alleviating glomerular and tubular injury in DKD rats，alleviating early renal hyperfiltration，and its mechanism may be related to the regulation of tubuloglomerular feedback |
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