摘要
目的探讨黄芪颗粒联合微RNA(miR)-30a对肾病综合征小鼠内质网应激、炎症水平和有丝分裂原活化蛋白激酶(MAPK)蛋白表达的影响。方法将50只小鼠随机分为对照组(n=10)和模型组(n=40)。模型组小鼠经尾静脉注射阿霉素溶液(7.5 mg·kg^(-1))制备原发性肾病综合征(PNS)模型,对照组小鼠经尾静脉注射等体积的生理盐水。造模成功后将模型组小鼠随机分为PNS组、黄芪组、miR-30a组和黄芪+miR-30a组,每组10只。黄芪组小鼠灌胃黄芪颗粒冲剂(20 mg·g^(-1)),每日2次;miR-30a组小鼠经尾静脉注射miR-30a antagomir(10 mg·kg^(-1)),每周1次;黄芪+miR-30a组小鼠灌胃黄芪颗粒冲剂(20 mg·g^(-1),每周1次),同时经尾静脉注射miR-30a antagomir(10 mg·kg^(-1));模型组和对照组小鼠灌胃与黄芪组等量的生理盐水,每日1次;各组小鼠均干预4周。于给药0、2、4周时检测各组小鼠24 h尿蛋白;于末次给药24 h后,应用全自动生物化学分析仪检测各组小鼠血清中总胆固醇(TC)、三酰甘油(TG)、血尿素氮(BUN)和血肌酐(Scr)水平,采用酶联免疫吸附试验法检测各组小鼠血清中白细胞介素(IL)-6、IL-8和肿瘤坏死因子-α(TNF-α)水平,苏木精-伊红染色观察各组小鼠肾组织病理学变化,免疫组织化学法检测各组小鼠肾组织中糖调节蛋白-78(GRP-78)和激活转录因子6(ATF6)的表达,Western blot法检测各组小鼠肾组织中GRP-78、ATF6、p38丝裂原活化蛋白激酶(p38 MAPK)、磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)、线粒体外活化蛋白激酶(ERK)、磷酸化线粒体外活化蛋白激酶(p-ERK)蛋白表达。结果PNS组、黄芪组、miR-30a组和黄芪+miR-30a组小鼠给药0、2、4周时24 h尿蛋白显著高于对照组(P<0.05)。给药2、4周时,黄芪组、miR-30a组和黄芪+miR-30a组小鼠的24 h尿蛋白显著低于PNS组(P<0.05);黄芪组与miR-30a组小鼠的24 h尿蛋白比较差异无统计学意义(P>0.05);黄芪+miR-30a组小鼠24 h尿蛋白显著低于
Objective Effect of Huangqi granules combined with microRNA(miR)-30a on endoplasmic reticulum stress,inflammatory levels and mitogen-activated protein kinase(MAPK)protein expression in mice with nephrotic syndrome.Methods Fifty mice were randomly divided into control group(n=10)and model group(n=40).The mice in the model group were intravenously injected with adriamycin solution(7.5 mg·kg^(-1))to establish primary nephrotic syndrome(PNS)model,the mice in the control group were intravenously injected with equivalent volume of physiological saline.After successful modeling,the mice in the model group were randomly divided into the PNS group,Huangqi group,miR-30a group and Huangqi+miR-30a group,with 10 mice in each group.The mice in Huangqi group were given Huangqi particles(20 mg·g^(-1))by gavage twice a day;the mice in miR-30a group were intravenously injected with miR-30a antagomir(10 mg·kg^(-1))once a week;the mice in Huangqi+miR-30a group were given Huangqi particles(20 mg·g^(-1))by gavage once a week and intravenously injected with miR-30a antagomir(10 mg·kg^(-1))at the same time;the mice in the model group and control group were given equivalent volume of physiological saline by gavage once a day;all mice were treated for 4 weeks.At 0,2 and 4 weeks of administration,the levels of 24-hour urinary protein of mice in each group were detected.At 24 hours after the last administration the serum total cholesterol(TC),triglycerides(TG),blood urea nitrogen(BUN),serum creatinine(Scr)levels of mice in each group were measured by automatic biochemical analyzer;the levels of interleukin(IL)-6,IL-8 and tumor necrosis factor-α(TNF-α)in serum of mice in each group were detected by enzyme-linked immunosorbent assay;the renal pathological changes of mice in each group were observed by hematoxylin-eosin staining;the expressions of glucose-regulated protein-78(GRP-78)and activating transcription factor 6(ATF6)in renal tissues of the mice in each group were detected by immunohistochemistry;the expressions of GRP-78,ATF6,p
作者
徐瑞
张晓
刘文霞
XU Rui;ZHANG Xiao;LIU Wenxia(Department of PediatricsⅢ,Nanyang First People′s Hospital,Nanyang 473000,Henan Province,China)
出处
《新乡医学院学报》
CAS
2023年第11期1008-1015,共8页
Journal of Xinxiang Medical University
