归肾经方对慢性肾纤维化大鼠β-Catenin、Col1、LN表达的影响  

Effects of the Prescription of Kidney Meridian on the Expression of β-Catenin, Col1,LN in Rats with Chronic Renal Fibrosis

作　　者：郑小利[1] 黄招兰[1] 胡姗姗 艾萌 吴文莉[2] 谢岱[2] 马威[2] Zheng Xiaoli;Huang Zhaolan;Hu ShanShan;Ai Meng;Wu Wertin;Xie Dai;Ma Wei(The Hospital of Wuhan University of Science and Technology, Wuhan 430065, China;Wuhan Integrated Traditional Chinese and Western Medicine Hospital, Wuhan 430030, China)

机构地区：[1]武汉科技大学医院,武汉430065 [2]武汉市中西医结合医院,武汉430030

出　　处：《世界科学技术-中医药现代化》2019年第5期994-1001,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家中医药管理局2010年中医药部门公共卫生专项(国中医药人教发(2010)59号)：2010年全国名老中医药专家传承工作室建设项目，负责人：朱宏斌;湖北省科技厅湖北省自然科学基金面上项目(2016CFC751)：从Wnt经典通路探讨辨疾病归经选药优化组方对肾纤维化模型干预作用研究，负责人：郑小利;武汉科技大学青年科技骨干培育计划(2016xz038)：从Wnt经典通路探讨辨疾病归经选药优化组方对肾纤维化模型干预作用研究，负责人：郑小利

摘　　要：目的:观察归经组方对肾纤维化进程干预的疗效及肾组织Wnt经典信号基因表达的影响。方法:用5/6肾切除方法建立大鼠肾纤维化模型。以经验方肾衰Ⅰ号为B组,治则相同不归肾经药物组方为A组,以治则相同归肾经的组方为C组,同时设模型组(model group),假手术组(sham group)。连续治疗2月后,采血检测肾功能及血色素、RT-PCR方法检测肾组织Wnt2、GSK-3β、β-Catenin组织肾功、LN、Col1a1 mRNA表达,免疫组化法(Immunohistochemistry,IHC)检测LN、COL1在肾组织表达。结果:治疗2月时,与假手术组比较,模型组质量、血色素(Hemoglobin,Hb)含量显著降低(P <0.01),血尿素氮(Blood Urea nitrogen,BUN)、肌酐(Creatinine,Cr)及24小时尿蛋白(24 hour urine protein,24hUPr)定量显著增高(P <0.01),Wnt2、GSK-3β、β-Catenin、LN、Col1a1 mRNA表达均显著增高(P <0.01),LN、COL1蛋白表达(IHC)显著增高(P <0.05);与模型组比较,各治疗组体重、Hb显著增高(P <0.01),BUN、Cr、24 h尿蛋白含量均显著降低(P <0.01),Wnt2、GSK-3β、β-Catenin均显著降、LN、Col1a1 mRNA表达显著降低(P <0.01),LN蛋白表达(IHC)显著降低(P <0.05),C组COL1蛋白表达显著降低(P <0.05);与C组比较,A、B组Hb显著降低(P <0.05)。结论:经验方、归肾经方和不归肾经方均能通过调控Wnt经典通路相关基因表达减缓肾纤维化进程,归肾经方在改善动物贫血状态上较优。Objective: To observe the effects of meridian tropism prescription on renal fibrosis progression and the gene expression of Wnt classical signaling in kidney. Methods: Renal fibrosis model was established by 5/6 nephrectomy in rats. The treatment group of empirical prescription was group B, prescription that made of medicines which do not belong to kidney meridian and the same therapeutic principle was group A, prescription that made of medicines which belong to kidney meridian and the same therapeutic principle was group C, model group and sham operation group were also set up. After 2 months’ continued therapy, blood was collected from abdominal aorta for testing kidney function and hemoglobin. The expression of Wnt2, GSK-3β,β-Catenin, LN, Col1 a1 mRNA was tested by RT-PCR, and the expression of LN, COL1 protein was tested by immunohistochemistry(IHC). Results: After 2 months of treatment,compared with the sham operation group, weight and hemoglobin(Hb) of the model group reduced significantly(P <0.01). Blood Urea nitrogen(BUN), creatinine(Cr) and 24 hour urine protein(24 hUPr) increased significantly(P < 0.01).The expression of Wnt2, GSK-3β,β-Catenin, LN, Col1 a1 mRNA increased obviously(P < 0.01) and the expression of LN, COL1(IHC) increased significantly(P < 0.05). Compared with the model group, weight and Hb significantly increased in each treatment group(P < 0.01), and BUN, Cr, 24 hUPr decreased obviously(P < 0.01). Wnt2, GSK-3β,β-Catenin, LN, Col1 a1 mRNA decreased(P < 0.01), and the expression of LN(IHC) decreased(P < 0.01). The expression of COL1(IHC) in group C decreased(P < 0.05). Compared with group C, Hb of group A and B increased significantly(P < 0.05). Conclusion: All of the empirical prescription, the prescription of meridian and the prescription of nonmeridian could slow the progression of renal fibrosis by regulating the gene expression of Wnt classical pathway, and the prescription of meridian was better in improving nutrition and anemia than the other groups.

关 键 词：归经 肾纤维化 wnt2 动物模型 大鼠 

分 类 号：R256[医药卫生—中医内科学]