雷公藤甲素对盐敏感性高血压所致小鼠肾损害的抑制作用研究  

Inhibitory effect and mechanisms of triptolide on salt-sensitive hypertension-induced renal injury of mice

作　　者：张诗雨 高攀 宋纯东 谢世阳 高原 王幼平 ZHANG Shi-yu;GAO Pan;SONG Chun-dong;XIE Shi-yang;GAO Yuan;WANG You-ping(Central Laboratory and Center for Cardiology,First College of Clinical Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan Province,China)

机构地区：[1]河南中医药大学第一临床医学院中心实验室及心脏中心,河南郑州450000

出　　处：《中国临床药理学杂志》2021年第23期3223-3227,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金面上基金资助项目(82074194,81673734)。

摘　　要：目的研究雷公藤甲素对盐敏感性高血压所致小鼠肾损害的作用及相关机制。方法按照体质量将小鼠随机分为4组:对照组、模型组和低、高2个剂量实验组,每组7~8只。用切除小鼠左肾、皮下植入醋酸脱氧皮质酮和饮用盐水法建立盐敏感性高血压小鼠模型,而对照组摘除左肾并正常饮水。造模后,低、高2个剂量实验组给予雷公藤甲素30和90μg·kg^(-1)(溶于二甲亚砜中进行腹腔注射),模型组给予等量二甲亚砜,每天1次,连续5周。观察各组小鼠尾动脉收缩压、肌酸酐清除率、肾组织病理学改变及单核/巨噬细胞介导的炎症反应。结果给药后,对照组、模型组和高剂量实验组的收缩压分别为(108.18±19.23),(150.61±19.24),和(154.61±19.21)mmHg^(-1)这3组的肌酸酐清除率分别为(347.44±24.68),(129.29±18.49),和(294.89±26.13)mL/24 h;这3组的肾小球硬化指数分别为0.09±0.04,0.70±0.11和0.32±0.07;这3组的肾小管间质损伤分数分别为0.34±0.16,3.41±0.51和1.48±0.31;这3组的肾单核/巨噬细胞浸润的数量分别为(8.40±1.40),(65.80±9.55)和(16.80±4.75)cell·mm;这3组的核转录因子-κB(NF-κB)的活性分别为(20.73±2.41),(58.86±5.15)和(25.20±4.07)ng·mg^(-1)。除收缩压外,模型组的上述指标与对照组相比,或实验组的上述指标与模型组相比,差异均有统计学意义(均P<0.05),且雷公藤甲素的作用呈剂量依赖性。结论雷公藤甲素通过抑制单核/巨噬细胞浸润为主的炎症反应减轻和缓解盐敏感性高血压所致的肾损害,且该作用为血压非依赖性的。Objective To determine the effects of triptolide on saltsensitive hypertension-induced renal injury and to identify the possible mechanisms in mice.Methods The mice were assigned into four groups according to weight:Control group,model group,and experimental-L(low-dose)group and experimental-H(high-dose)group,each group consisted of 7-8 mice.A mouse model of salt-sensitive hypertension was established by the excision of left kidney,subcutaneous implantation of deoxycorticosterone acetate and administration of saline to drink,but the moce in control group was only excision of left kidney and normal drinking water.After modeling,mice in model group was injected intraperitoneally with dimethyl sulfoxide,and experimental-L group and experimental-H group were injected intraperitoneally with 30 or 90μg·kg^(-1)triptolide,once a day for five weeks.At the end of experiment,tail-cuff systolic blood pressure,creatinine clearance,renal changes in pathology,and monocyte/macrophage-mediated inflammatory response were determined in all groups.Results After treatment,systolic blood pressure in control group,model group,and experimental-H group were(108.18±19.23),(150.61±19.24)and(154.61±19.21)mm Hg^(-1)the creatinine clearance in the three groups were(347.44±24.68),(129.29±18.49)and(294.89±26.13)m L/24 h;the glomerulosclerosis index in the three groups were 0.09±0.04,0.70±0.11 and 0.32±0.07;the tubulointerstitial injury score in the three groups were(0.34±0.16),(3.41±0.51)and(1.48±0.31)point;the number of renal infiltrated monocytes/macrophages in the three groups were(8.40±1.40),(65.80±9.55)and(16.80±4.75)cell·mm;and the renal nuclear factor-κB(NF-κB)activity in the four groups were(20.73±2.41),(58.86±5.15)and(25.20±4.07)ng·mg^(-1).Compared between model group and control group,or experimental group and model group,the differences of the parameters were statistically significant with the exception of systolic blood pressure(all P<0.05).Moreover,triptolide dose-dependently protected against renal injury i

关 键 词：雷公藤甲素 盐敏感性高血压 肾损害 单核/巨噬细胞 炎症 

分 类 号：R28[医药卫生—中药学]