机构地区:[1]南京中医药大学附属常州市中医医院,常州213000
出 处:《世界科学技术-中医药现代化》2018年第2期281-287,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基 金:江苏省常州市科技局项目(CJ20160042):基于Wnt/β-catenin信号通路的保元排毒丸延缓UUO大鼠肾纤维化的机理研究;负责人:王身菊
摘 要:目的:观察保元排毒丸对单侧输尿管梗阻(Unilateral Ureteral Obstruction UUO)模型大鼠肾脏病理的影响及对Wnt/β-catenin信号转导通路的调控。方法:48只健康清洁级雄性SD大鼠,随机分为假手术组、UUO组、厄贝沙坦组(12.5g·kg-1/天)、保元排毒丸低、中、高剂量组(1.25g·kg-1/天、2.5g·kg-1/天、5.0g·kg-1/天),每组8只;除假手术组只分离输尿管不结扎外其余均制备右侧输尿管梗阻肾纤维化模型,造模第二天开始予相应的药物灌胃,假手术组和UUO组给予自由进食和生理盐水灌胃,共灌14天。末次灌胃24小时后取右肾进行HE染色观察肾脏病理改变,Masson染色观察肾组织胶原沉积情况;Western Blot法测肾组织E-cadherin、Collagen I、β-Catenin表达水平;Real-time PCR检测Wnt4、β-catenin m RNA表达。结果:与假手术组比较,UUO组和各给药组肾小管、肾间质病变重、肾纤维化重(P<0.01);与UUO组比较,保元排毒丸低、中、高剂量组和厄贝沙坦组肾小管、肾间质病变明显减轻、肾纤维化减轻(P<0.01);UUO组E-cadherin表达较保元排毒丸各剂量组、厄贝沙坦组和假手术组明显减少(P<0.01);保元排毒丸各剂量组和厄贝沙坦组Collagen I、β-Catenin表达明显少于UUO组(P<0.01);UUO组Wnt4、β-catenin m RNA表达明显高于假手术组(P<0.01),保元排毒丸各剂量组和厄贝沙坦组Wnt4、β-catenin m RNA表达明显低于UUO组(P<0.01)。结论:保元排毒丸有改善肾脏纤维化的作用,其机理可能与调控Wnt/β-catenin信号转导通路有关。This study was aimed to investigate the pathological influence and effect of Bao-Yuan Pai-Du(BYPD) pill on Wnt/β-catenin signaling pathway in renal fibrosis of unilateral ureteral obstruction(UUO) rats. A total of 48 male Sprague Dawley rats were randomly divided the sham-operation group, UUO group, irbesartan group(12.5 g·kg^(-1)·d^-1),low-dose(1.25 g·kg^(-1)·d^-1), medium-dose(2.5 g·kg^(-1)·d^-1), and high-dose(5.0 g·kg^(-1)·d^-1) BYPD group, with 8 rats in each group. Ureter of rats in the sham-operation group was only separated without ligation. Renal fibrosis rat model was prepared by unilateral ureteral obstruction on the right side among other rats. Intragastric administration of corresponding drug was given from the second day after the model was established. Intragastric administration of physiological saline was given to rats in the sham-operation group and UUO group. The intragastric administration was given for 14 days. The right kidney was collected for pathological examinations 24 h after the last intragastric administration. Pathological changes of obstruction renal tissues were examined by Hematoxylin and Eosin(HE) staining and Masson staining.Protein expression of E-cadherin, Collagen I and β-catenin were detected by Western blot method. Real-time PCR was used to detect m RNA expressions of wnt4 and β-catenin. The results showed that compared with the sham-operation group, renal tubule, renal tubulointerstitial disease and renal fibrosis became severe in the UUO group and other medication groups(P〈0.01). Compared with the UUO group, renal tubule, renal tubulointerstitial disease and renal fibrosis were significantly reduced in the low-dose, medium-dose, high-dose BYPD group as well as the irbesartan group(P〈0.01). The expression of E-cadherin in the UUO group was significantly reduced compared with that in different dose BYPD groups and the irbesartan group(P〈0.01). Expressions of Collagen I and β-Catenin of different dose
关 键 词:保元排毒丸 肾纤维化 单侧输尿管梗阻 WNT/Β-CATENIN
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