火绒草联合黄芪对系膜增生性肾小球肾炎模型大鼠肾功能的改善作用及机制研究
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篇名: 火绒草联合黄芪对系膜增生性肾小球肾炎模型大鼠肾功能的改善作用及机制研究
TITLE: Study on the Improvement Effects and Mechanism of Leontopodium leontopodioides Combined with Astragalus membranaceus on Renal Function of MsPGN Model Rats
摘要: 目的:研究火绒草联合黄芪对系膜增生性肾小球肾炎(MsPGN)模型大鼠肾功能的改善作用及其可能机制。方法:将85只大鼠按体质量随机分为假手术组(n=10)和造模组(n=75)。假手术组大鼠行假手术,造模组大鼠采用免疫学方法(弗氏佐剂+牛血清蛋白+脂多糖)复制MsPGN模型。选取造模成功的70只大鼠,按体质量随机分为模型组,火绒草+黄芪高、中、低剂量组(4.05、2.03、1.02g/kg,以生药总量计),火绒草单用组(2.70g/kg,以生药量计),雷公藤多苷片组(阳性对照1,0.02g/kg)和盐酸贝那普利片组(阳性对照2,0.02g/kg),每组10只。假手术组和模型组大鼠灌胃等体积生理盐水,各给药组大鼠灌胃相应药液,每天给药1次,灌胃体积均为15mL/kg,连续给药5周。末次给药后,测定大鼠24h尿蛋白、尿肌酐和血肌酐水平;称定右侧肾质量并采用苏木精-伊红染色法观察肾组织病理形态学变化;采用免疫组化法检测肾组织中核转录因子-κBp65(NF-κBp65)蛋白表达水平;采用Westernblotting法测定肾组织中NF-κB、NF-κB抑制蛋白α(IκBα)、细胞外调节蛋白激酶(ERK)、磷酸化ERK(p-ERK)、p38丝裂原活化蛋白激酶(p38MAPK)蛋白表达水平。结果:与假手术组比较,模型组大鼠右侧肾质量、24h尿蛋白、血肌酐水平以及肾组织中NF-κBp65、p-ERK、p38MAPK蛋白表达水平均显著升高(P<0.05或P<0.01);尿肌酐水平和肾组织中IκBα蛋白表达水平均显著降低(P<0.05或P<0.01);肾组织出现肾小球明显肥大、系膜区细胞弥漫性增多、肾小管坏死等病理形态学变化。与模型组比较,火绒草单用组大鼠右侧肾质量、血肌酐水平均显著降低(P<0.05),尿肌酐水平显著升高(P<0.05),但24h尿蛋白水平差异无统计学意义(P>0.05);火绒草+黄芪高剂量组大鼠右侧肾质量、24h尿蛋白、血肌酐水平以及肾组织中NF-κBp65、p-ERK、p38MAPK蛋白表达水平均显著降低(P<0.05),尿肌酐水平和肾组织中IκBα蛋白表达水平均显著升高(P<0.05或P<0.01);火绒草+黄芪中、低剂量组大鼠上述指标差异均无统计学意义(P>0.05);各给药组大鼠肾组织病理变化均得到不同程度的改善,并以火绒草+黄芪高剂量组改善较明显。结论:高剂量火绒草+黄芪可通过抑制MAPK/NF-κB信号途径达到改善MsPGN模型大鼠肾功能的作用。
ABSTRACT: OBJECTIVE:To study the improvement effect and possible mechanism of Leontopodium leontopodioides combined with Astragalus membranaceus on the renal function of mesangial proliferative glomerulonephritis (MsPGN) model rats. METHODS:Totally 85 rats were randomly divided into sham operation group (n=10)and modeling group (n=75). Sham operation group underwent sham operation ,and MsPGN model was induced by immunological method [Freund ’s adjuvant+BSA + lipopolysaccharide(LPS)] in modeling group. After successfully modeling ,70 rats were randomly divided into model group ,L. leontopodioides+A. membranaceus high-dose,medium-dose and low-dose groups (4.05,2.03,1.02 g/kg,by total crude drug ),L. leontopodioides alone group (2.70 g/kg,by crude drug ),Tripterygium glycosides tablet group (positive control 1,0.02 g/kg), Lotensin tablet group (positive control 2,0.02 g/kg),with 10 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically ; administration groups were given relevant drug solution intrasgastrcially at a volume of 15 mL/kg,once a day ,for consecutive 5 weeks. At last administration ,24 h urinary lnzyxyqy2003@163.com protein,urine creatinine and serum creatinine were determined in rats. The right kidney was weighed ,and HE staining was used to observe the pathomorpholog y changes of renal tissue. Immunohistochemistry was used to detect the protein expression of NF-κB p65 in renal tissue. Western blotting assay was used to determine the protein expressions of NF-κB p65,IκBα,ERK,p-ERK and p 38 MAPK in renal tissue. RESULTS :Compared with sham operation group ,right kidney weight ,24 h urine protein and serum creatinine levels ,protein expressions of NF-κB p65, p-ERK and p 38 MAPK in renal tissue were increased significantly in model group (P<0.05 or P<0.01);the level of urine creatinine and protein expression of IκBα in renal tissue were decreased significantly(P<0.05 or P<0.01);there were obvious glomerular hypertrophy ,diffuse increase of mesangial cells ,necrosis of renal tubules and other pathomorphological changes in renal tissue. Compared with model group ,right kidney weight and serum creatinine level were decreased significantly in L. leontopodioides alone group (P<0.05),while urine creatinine level was increased significantly (P<0.05),but there was no statistical significance in the level of 24 h urine protein (P>0.05);the right kidney weight ,24 h urine protein ,serum creatinine level and protein expression levels of NF-κB p65,p-ERK and p38 MAPK in renal tissue were decreased significantly in L. leontopodioides+A. membranaceus high-dose group (P<0.05),while the urine creatinine level and protein expression level of IκBα in renal tissue were increased significantly (P<0.05 or P<0.01);there was no statistical significance in above indexes in L. leontopodioides+A. membranaceus medium-dose,low-dose groups (P>0.05);pathological changes of renal tissue were improved to different extents in administration groups ,especially in L. leontopodioides +A. membranaceus high-dose group. CONCLUSIONS : High dose of L. leontopodioides +A. membranaceus can improve renal function of MsPGN model rats by inhibiting MAPK/NF-κB signal pathway.
期刊: 2020年第31卷第15期
作者: 齐越,仲坤,贾冬,李荧,袁龙,黄培池,单舒筠,杨彩瑜,高侠
AUTHORS: QI Yue, ZHONG Kun,JIA Dong,LI Ying,YUAN Long,HUANG Peichi,SHAN Shujun,YANG Caiyu,GAO Xia
关键字: 火绒草;黄芪;系膜增生性肾小球肾炎;炎症;肾功能;机制;p38丝裂原活化蛋白激酶;核转录因子-κB;大鼠
KEYWORDS: Leontopodium leontopodioides ; Astragalus membranaceus ; Mesangial proliferative glomerulonephritis ;
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