盐炙杜仲对大鼠肾阳虚的影响及机制研究  

Study on the effects and mechanism of saltwater stir-baked Eucommia ulmoides on kidney-yang deficiency in rats

作　　者：程芬[1] 杨长花[1] 宋艳丽[1] 杜蓓[1] 刘峰[1,2] 胡本祥 CHENG Fen;YANG Changhua;SONG Yanli;DU Bei;LIU Feng;HU Benxiang(College of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xi’an 712046,China;Shaanxi Buchang Pharmaceutical Co.,Ltd.,Xi’an 710075,China;College of Pharmacy,Shaanxi University of Chinese Medicine,Xi’an 712046,China)

机构地区：[1]陕西国际商贸学院医药学院,西安712046 [2]陕西步长制药有限公司,西安710075 [3]陕西中医药大学药学院,西安712046

出　　处：《中国药房》2022年第12期1460-1465,共6页China Pharmacy

基　　金：陕西省教育厅科学研究专项计划项目(No.16JK2033);陕西省中药绿色制造技术协同创新中心省级科研平台项目(No.2019XT-3-05);陕西高校青年科技创新团队项目(No.陕教[2019]90号)。

摘　　要：目的研究盐炙杜仲对大鼠肾阳虚的影响及潜在机制。方法将90只SD大鼠随机分为正常对照组(15只)和造模组(75只),造模组大鼠灌胃腺嘌呤建立肾阳虚大鼠模型;造模完成后,将其随机分为模型组、阳性对照组(桂附地黄片2.5 g/kg)和盐炙杜仲低、中、高剂量组(1.5、3、6 g/kg),每组15只。各药物组大鼠灌胃相应药液,正常对照组和模型组大鼠灌胃生理盐水,每天1次,连续给药8周。称定各组大鼠建模前和给药结束后的体质量,并于给药结束后进行肾阳虚症候评分,检测其血清中血尿素氮(BUN)、血肌酐(SCR)、睾酮(T)、皮质醇(COR)水平,肾组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平;经苏木精-伊红染色后观察其肾组织病理变化,采用实时定量聚合酶链反应检测其肾组织中缺氧诱导因子1α(HIF-1α)、信号转导及转录活化因子蛋白5(STAT5)mRNA的相对表达量,采用Western blot法检测其肾组织中HIF-1α、STAT5、磷酸化STAT5(p-STAT5)蛋白的相对表达量和p-STAT5与STAT5的灰度值比值(p-STAT5/STAT5)。结果建模前,各组大鼠体质量比较,差异无统计学意义(P>0.05)。给药结束后,与模型组比较,盐炙杜仲各剂量组和阳性对照组大鼠肾组织病理改变均有所恢复,其体质量、血清T水平及肾组织中SOD活性均显著升高(P<0.05),肾阳虚症候评分,血清中BUN、SCR、COR水平,肾组织中MDA水平,HIF-1α、STAT5mRNA和HIF-1α、STAT5、p-STAT5蛋白的相对表达量,以及p-STAT5/STAT5均显著降低(P<0.05),且盐炙杜仲的上述作用有剂量依赖性(P<0.05)。结论盐炙杜仲能明显缓解肾阳虚大鼠的肾组织损伤,降低血清中BUN、SCR、COR水平,升高血清中T水平,其机制可能与抗氧化应激、抑制HIF-1α和STAT5蛋白的表达有关。OBJECTIVE To study the effects and potential mechanism of saltwater stir-baked Eucommia ulmoides on kidneyyang deficiency in rats. METHODS Ninety SD rats were randomly divided into normal control group(15 rats) and modeling group(75 rats). Modeling group was given adenine intragastrically to establish kidney-yang deficiency model. After modeling,modeling group were randomly divided into model group,positive control group(Guifu dihuang tablet 2.5 g/kg),low-dose,medium-dose and high-dose groups of saltwater stir-baked E. ulmoides(1.5,3,6 g/kg),with 15 rats in each group. Administration groups were given relevant medicine intragastrically, normal control group and model group were given normal saline intragastrically,once a day,for consecutive 8 weeks. The body weight of rats was measured before modeling and after medication.The score of kidney-yang deficiency syndrome was performed after medication. The levels of blood urea nitrogen(BUN),serum creatinine(SCR),testosterone(T) and cortisol(COR) in serum and superoxide dismutase(SOD) activity,malondialdehyde(MDA) level in renal tissue were detected. The pathological changes of renal tissue were observed after HE staining. Relative expressions of hypoxia-inducible factor-1α (HIF-1α) and signal transducer and activator of transcription 5(STAT5) mRNA in renal tissue were detected by RT-PCR. The relative expressions of HIF-1α,STAT5 and phosphorylated STAT5(p-STAT5)protein and the ratio of gray values of p-STAT5 and STAT5(p-STAT5/STAT5)in renal tissue were detected by Western blot. RESULTS Before modeling,there was no statistical significance in body weight of rats in each group(P>0.05). After medication,compared with model group,pathological changes of renal tissue were all recovered in saltwater stir-baked E. ulmoides groups and positive control group,while body weight,the level of T in serum and SOD activity in renal tissue were all increased significantly(P<0.05). The scores of kidney-yang deficiency syndrome,levels of BUN,SCR and COR in serum,MDA level in renal tis

关 键 词：盐炙杜仲 肾阳虚 大鼠 缺氧诱导因子1Α 信号传导及转录活化因子5 

分 类 号：R965[医药卫生—药理学]