摘要
目的:基于代谢组学方法,探索小檗皮对STZ诱导糖尿病肾病(DN)大鼠的保护机制,发现相关血清代谢标志物。方法:腹腔注射小剂量链脲佐菌素(STZ)复制DN大鼠模型,造模成功后,分别灌胃给予小檗皮0.7 g/kg水浸膏组、盐酸小檗碱+盐酸小檗胺171 mg/kg+48 mg/kg组和二甲双胍0.196 g/kg组,空白组和模型组给予等体积的生理盐水,每天1次,连续4周,同时检测空腹血糖水平(FBG)。采集大鼠血清检测血尿素氮(BUN)、肌酐(Scr)、尿酸(UA)、总蛋白(TP)、转换生长因子-β1(TGF-β1)和血管内皮生长因子(VEGF)的含量,电镜下观察肾脏病理形态学变化及测定肾小球基底膜厚度。同时,大鼠血清采用LC-MS代谢组学技术,主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)等方法筛选并鉴定与DN相关的生物标志物,利用MetPa数据库分析相关代谢通路。结果:与空白组相比,模型组血清FBG、BUN、Scr、UA、TGF-β1和VEGF显著升高,TP显著降低;与模型组相比,给药组血清FBG、BUN、Scr、UA、TGF-β1和VEGF明显降低,TP显著升高;电镜结果表明给药组均能改善大鼠肾组织病理损伤,减少肾小球基底膜厚度。代谢组学结果表明给药组的代谢物能够显著区分,发现并初步鉴定了17个差异代谢物及6条相关通路。结论:小檗皮能够改善DN的病理变化和药效学指标,其作用机制可能为上调DN大鼠血清中的鸟氨酸含量,参与精氨酸与脯氨酸的代谢,而盐酸小檗碱、盐酸小檗胺可能是小檗皮发挥治疗DN作用的物质基础。
Objective:To study the protective effect and mechanism of Berberidis dictyophyllae Cortex on STZ induced diabetic nephropathy(DN)rat,and to discover the relative metabolic markers in serum.Methods:DN rat model was established by intraperitoneal injection of streptozotocin(STZ).Then Berberidis dictyophyllae Cortex extractum(0.7 g/kg),berberine hydrochloride+berbamine hydrochloride(171 mg/kg+48 mg/kg)and metformin(0.196 g/kg)were administered,rats in the control and the model group were given equal volume of normal saline once a day for 4 weeks.The level of FBG was determined.Rat serum was collected to detect the contents of blood urea nitrogen(BUN),creatinine(Scr),uric acid(UA),total protein(TP),transforming growth factor-beta 1(TGF-β1)and vascular endothelial growth factor(VEGF).The pathological morphological changes of the kidney and the thickness of the glomerular basement membrane were observed under electron microscope.Meanwhile,DN related biomarkers in rats serum were screened and identified by LC-MS metabolomics,principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA).And relevant metabolic pathways were analyzed by MetPa database.Results:Pharmacodynamic results showed that compared with the control group,the levels of blood glucose,BUN,Scr,UA,TGF-β1 and VEGF were significantly increased and TP was significantly decreased in the model group.Compared with the model group,the levels of blood glucose,BUN,Scr,UA,TGF-beta 1 and VEGF were significantly decreased,the level of TP was significantly in the drug administration groups.The electron microscopy results showed that the drug administration groups improved the renal histopathological injury and reduced the thickness of glomerular basement membrane.The metabolites in the drug administration groups were distinctly distinguished,17 different metabolites and 6 related pathways were observed and preliminarily identified.Conclusion:Berberidis dictyophyllae Cortex treatment can ameliorat the pathological injury and pharmacodynamics of DN.Its mechanism may be related to up-regulating the content of ornithine in DN rat serum and participating in the metabolism of arginine and proline.Berberine hydrochloride and berbamine hydrochloride may be the material basis of Berberidis dictyophyllae Cortex in the treatment of DN.
作者
艾小鹏
王小博
王小艳
侯娅
梁雨生
黄婉奕
杜明胜
范刚
童东
赖先荣
孟宪丽
Ai Xiaopeng;Wang Xiaobo;Wang Xiaoyan;Hou Ya;Liang Yusheng;Huang Wanyi;Du Mingsheng;Fan Gang;Tong Dong;Lai Xianrong;Meng Xianli(Chengdu University of Traditional Chinese Medicine,Chengdu 611137)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第2期67-73,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金(81473427、81774007、81173360、81560806)
国家重点研发计划“民族医药发掘整理与学术传承研究”(2017YFC1703904)
四川省教育厅重点项目(16ZA0120)
青海省科技计划项目(2017-ZJ-922Q)
关键词
小檗皮
糖尿病肾病
代谢组学
保护机制
Berberidis dictyophyllae Cortex
diabetic nephropathy
defense mechanisms
metabolomics
作者简介
通讯作者:赖先荣,教授,E-mail:vegf@cdutcm.edu.cn;通讯作者:孟宪丽,教授,E-mail:xlm999@cdutcm.edu.cn;艾小鹏,硕士研究生,E-mail:694010570@qq.com。
