CAJ | 학술논문

目的：观察黄芪丹参颗粒药对对肾纤维化信号通路Wnt/β-catenin的影响，并初步明确其量效关系。方法：40只雄性SD大鼠，随机分为5组，即正常组，模型组，黄芪丹参颗粒药对（1：1）低剂量治疗组，黄芪丹参颗粒药对（1：1）中剂量治疗组，黄芪丹参颗粒药对高剂量（1：1）治疗组。除正常组外，其余大鼠均建立单侧输尿管梗阻（UUO）模型。各组给予相应药物治疗，收集尿液检测24 h尿蛋白、α1-微球蛋白（α1-Microglobulin ，α1-MG）的含量，光镜观察肾组织病理；Western Blot技术检测肾组织Wnt4和β-catenin蛋白表达。结果：淤24 h尿蛋白和α1- MG检测结果，与正常组比较，模型组24 h尿蛋白和α1- MG均明显升高（P约0.05）；与模型组比较，各治疗组24 h尿蛋白和α1-MG明显降低（P约0.05）；与颗粒低剂量组比较，颗粒中、高剂量组24h尿蛋白均明显降低（P约0.05），各剂量组之间α1-MG差异无显著性。于HE染色结果，各治疗组病理变化较模型组均有明显改善，与颗粒低剂量组比较，颗粒中、高剂量组评分明显减少（P约0.05）。盂肾组织Wnt4和β-catenin免疫印迹检测结果，与正常组比较，模型组和各剂量组大鼠肾组织Wnt4和β-catenin具有明显有升高趋势，各治疗组均有不同程度下降，尤以颗粒中、高剂量组下降明显。结论：黄芪丹参（1：1）颗粒药对可以保护UUO大鼠肾小管功能，一定程度改善UUO大鼠肾脏病理改变，其机制可能与干预Wnt/β-catenin信号通路有关。黄芪丹参颗粒药对可以干预UUO大鼠肾组织中Wnt4、β-catenin的表达，并存在一定的量效关系。
목적：관찰황기단삼과립약대대신섬유화신호통로Wnt/β-catenin적영향，병초보명학기량효관계。방법：40지웅성SD대서，수궤분위5조，즉정상조，모형조，황기단삼과립약대（1：1）저제량치료조，황기단삼과립약대（1：1）중제량치료조，황기단삼과립약대고제량（1：1）치료조。제정상조외，기여대서균건립단측수뇨관경조（UUO）모형。각조급여상응약물치료，수집뇨액검측24 h뇨단백、α1-미구단백（α1-Microglobulin ，α1-MG）적함량，광경관찰신조직병리；Western Blot기술검측신조직Wnt4화β-catenin단백표체。결과：어24 h뇨단백화α1- MG검측결과，여정상조비교，모형조24 h뇨단백화α1- MG균명현승고（P약0.05）；여모형조비교，각치료조24 h뇨단백화α1-MG명현강저（P약0.05）；여과립저제량조비교，과립중、고제량조24h뇨단백균명현강저（P약0.05），각제량조지간α1-MG차이무현저성。우HE염색결과，각치료조병리변화교모형조균유명현개선，여과립저제량조비교，과립중、고제량조평분명현감소（P약0.05）。우신조직Wnt4화β-catenin면역인적검측결과，여정상조비교，모형조화각제량조대서신조직Wnt4화β-catenin구유명현유승고추세，각치료조균유불동정도하강，우이과립중、고제량조하강명현。결론：황기단삼（1：1）과립약대가이보호UUO대서신소관공능，일정정도개선UUO대서신장병리개변，기궤제가능여간예Wnt/β-catenin신호통로유관。황기단삼과립약대가이간예UUO대서신조직중Wnt4、β-catenin적표체，병존재일정적량효관계。
This study was aimed to observe the effect of Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma granules on Wnt/β-catenin signaling pathway of renal fibrosis in order to preliminary identify its dose-response relationship. A total of 40 male SD rats were randomly divided into 5 groups, which were the normal group, model group, low-dose group which the ratio of Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma of 1:1; middle-dose (1:1) group, and high-dose (1:1) group. Except the normal group, rats in other groups were established into the unilateral ureteral obstruction (UUO) rat models. Medication was given to each corresponding group. Urine was collected to determine the 24-hour urine protein and α1-microglobulin (α1-MG). Light microscope was used to observe pathological changes in renal tissues. Western blotting was used to detect expression of Wnt4 and β-catenin in renal tissues. The results showed that compared with the normal group, the levels of 24-hour urine protein andα1-MG were obviously increased (P < 0.05). Compared with the model group, the levels of 24-hour urine protein and α1-MG in each treatment group were obviously decreased (P < 0.05). Compared with the low-dose group, the level of 24-hour urine protein was obviously decreased than the middle-dose and high-dose group (P< 0.05). There were no significant differences on α1-MG among groups with different doses (P > 0.05). HE stain showed that pathological changes in each treatment group were obviously improved. Compared with the low-dose group, the scores of the middle-dose and high-dose group were obviously reduced (P< 0.05). The western blotting showed that compared with the normal group, the Wnt4 and β-catenin in renal tissues of rats in the model group and groups with different doses were obviously increased. There were different levels of decreasing in each treatment group. The decreasing was especially obvious in the middle-dose and high-dose group. It was concluded that the Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma (1:1) granules can protect renal tubular function in UUO rats. It can improve the renal pathological changes in UUO rats at certain level. The mechanism may relate to its interference with the Wnt/β-catenin signaling pathway. The Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma granules can intervene the expression of Wnt4 and β-catenin in renal tissues among UUO rats. There was some concentration-response relationship.