养肝益水颗粒对高血压早期肾损害大鼠AngⅡ/TRPC6/NF-κB通路的影响  

Effect of Yanggan Yishui Granules on AngⅡ/TRPC6/NF-κB Pathway in Rats with Early Renal Damage of Hypertension

作　　者：沈丹琪 戴小华[2] 杨帆 王银燕[2] 邵正斌[2] 付军[2] 冉永玲 袁良[2] SHEN Danqi;DAI Xiaohua;YANG Fan;WANG Yinyan;SHAO Zhengbin;FU Jun;RAN Yongling;YUAN Liang(Lu'an Chinese Medicine Hospital,Lu'an 237000 Anhui,China;First Hospital Affiliated to Anhui University of Traditional Chinese Medicine,Branch of National Clinical Research Center for Chinese Medicine Cardiology,Institution of Cardiovascular Disease,Anhui Academy of Chinese Medicine Sciences,Hefei 230031 Anhui,China)

机构地区：[1]六安市中医院,安徽六安237000 [2]安徽中医药大学第一附属医院,国家中医心血管病临床医学研究中心分中心,安徽省中医药科学院心血管病研究所,安徽合肥230031

出　　处：《中药新药与临床药理》2022年第2期187-193,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：安徽省中医药领军人才资助项目(中医药发展秘[2018]23号)。

摘　　要：目的观察养肝益水颗粒对高盐高脂饮食诱导高血压早期肾损害SD大鼠血管紧张素Ⅱ(AngⅡ)/瞬时受体电位阳离子通道6(TRPC6)/核转录因子-κB(NF-κB)通路的影响。方法将50只SD大鼠随机分为空白组、模型组、贝那普利组、养肝益水颗粒组、养肝益水颗粒+贝那普利组,每组10只。模型组、贝那普利组、养肝益水颗粒组、养肝益水颗粒+贝那普利组喂养高盐高脂饲料制备实验模型,周期为6周。6周后,贝那普利组给药贝那普利悬液(0.9 mg·kg^(-1)·d^(-1)),养肝益水颗粒组给药养肝益水颗粒悬液(2.7 g生药·kg^(-1)·d^(-1)),养肝益水颗粒+贝那普利组分别给药养肝益水颗粒悬液(2.7 g生药·kg^(-1)·d^(-1))、贝那普利混悬液(0.9 mg·kg^(-1)·d^(-1)),空白组、模型组灌胃相同量蒸馏水,周期为4周。每周监测大鼠血压值,给药前、后收集大鼠尿液测ACR(白蛋白与尿肌酐的比值)、β2-微球蛋白(β2-MG),留取大鼠血标本,检测血清中血肌酐(Scr)、尿素氮(BUN)、AngⅡ含量,留取大鼠双肾标本,观察大鼠肾脏组织病理变化,检测肾脏组织中AngⅡ、TRPC6、NF-κB等蛋白含量。结果与空白组对比,SD大鼠经高盐高脂饲料喂养6周后,模型组、贝那普利组、养肝益水颗粒组、养肝益水颗粒+贝那普利组收缩压、尿ACR、β2-微球蛋白、血清AngⅡ、肾脏组织AngⅡ、TRPC6、NF-κB蛋白表达水平均明显升高(P<0.01);给药4周后,与模型组相比,贝那普利组、养肝益水颗粒组、养肝益水颗粒+贝那普利组收缩压、尿ACR、β2-微球蛋白、血清AngⅡ、肾脏组织AngⅡ、TRPC6、NF-κB蛋白表达水平均明显降低(P<0.01);与贝那普利组相比,养肝益水颗粒组各检测指标较贝那普利组高,养肝益水颗粒+贝那普利组各检测指标较贝那普利组低。肾脏组织病理变化显示,空白组肾组织结构正常,模型组肾脏结构可见明显异常,贝那普利组、养肝益水颗粒组、养肝益水颗粒Objective To observe the effect of Yanggan Yishui granules on AngⅡ/TRPC6/NF-κB pathway in SD rats with early renal damage induced by high-salt and high-fat diet.Methods 50 SD rats were randomly divided into blank group,model group,benazepril group(ACEI group),Yanggan Yishui granules group(YGYS group),Yanggan Yishui granules+benazepril group(YGYS+ACEI group),10 rats per group.The model group,ACEI group,YGYS group,and YGYS+ACEI group were fed with high-salt and high-fat diet to prepare experimental models.The period was 6 weeks.After 6 weeks,the ACEI group was given benazepril suspension(0.9 mg·kg^(-1)·d^(-1)),the YGYS group was given Yanggan Yishui granules suspension(2.7 g crude drug·kg^(-1)·d^(-1)),and the YGYS+ACEI group was given Yanggan Yishui granules suspension(2.7 g crude drug·kg^(-1)·d^(-1)),benazepril suspension(0.9 mg·kg^(-1)·d^(-1)),respectively.The blank group and the model group were simultaneously given the same amount of distilled water.All groups were administered for 4 weeks.We monitored the blood pressure of rats every week,collected rat urinary to determine ACR(urinary albumin to creatinine ratio)andβ2-MG(β2-microglobulin)before and after administration.Blood specimens of rats were kept and subjected to detect the contents of SCR,BUN,AngⅡin serum.Kidney specimens of rats were collected for the observation of pathological changes and the detection of AngⅡ,TRPC6,NF-κB and other proteins.Results:Compared with the blank group,systolic blood pressure,urine ACR,β2-MG,serum AngⅡ,protein expressions of AngⅡ,TRPC6 and NF-κB in kidney tissue were significantly increased(P<0.01)in the model group,ACEI group,YGYS group and ACEI+YGYS group after SD rats were modeled for 6 weeks.Compared with the model group,systolic blood pressure,urine ACR,β2-MG,serum Ang II,protein expressions of AngⅡ,TRPC6,and NF-κB in kidney tissue were significantly reduced(P<0.01)in ACEI group,YGYS group and ACEI+YGYS group after 4 weeks of administration.Compared with ACEI group,the detection indexes of YG

关 键 词：养肝益水颗粒 高血压早期肾损害 AngⅡ/TRPC6/NF-κB通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]