摘要
目的:探讨穿心莲内酯对膜性肾病(MN)大鼠的保护作用。方法:选取清洁级健康雄性SD大鼠80只,设为正常组、模型组、穿心莲内酯组(穿心莲内酯50 mg/kg)和贝那普利组(盐酸贝那普利10 mg/kg),每组20只。模型组、穿心莲内酯组和贝那普利组大鼠通过尾静脉注射阳离子化牛血清白蛋白建立MN大鼠模型。穿心莲内酯组、贝那普利组大鼠分别连续4周灌胃给药,1日1次;正常组和模型组大鼠连续4周灌胃给予0.9%氯化钠溶液,1日1次。采用生化分析法检测肾功能指标水平;通过苏木精-伊红染色、Masson染色行肾组织病理学检查,通过透射电子显微镜(TEM)观察肾组织超微结构变化;采用酶联免疫吸附试验检测肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和细胞间黏附分子-1(ICAM-1)含量;采用蛋白质印迹法检测蛋白表达水平。结果:与模型组相比,穿心莲内酯组、贝那普利组大鼠肾组织病变和超微结构病变均明显减轻,其中穿心莲内酯组效果更为显著;24 h尿蛋白定量和肌酐(SCr)水平明显降低;TNF-α、IL-6和ICAM-1含量明显降低;Toll样受体4(TLR4),核因子κB(NF-κB),转化生长因子β1(TGF-β1),磷酸化Smad2、磷酸化Smad3,Ⅰ型和Ⅲ型胶原蛋白表达量明显降低,差异均有统计学意义(P<0.01)。且穿心莲内酯组大鼠上述指标水平明显优于贝那普利组,差异均有统计学意义(P<0.05或P<0.01)。结论:穿心莲内酯对MN大鼠肾纤维化具有抑制作用,可能与抑制TLR4/NF-κB通路和TGF-β1/Smad通路,降低炎症反应和细胞外基质生成有关。
OBJECTIVE:To investigate the protective effects of andrographolide on membranous nephropathy(MN)in rats.METHODS:Eighty clean healthy male SD rats were divided into the normal group,model group,andrographolide group(andrographolide 50 mg/kg)and benazepril group(benazepril hydrochloride 10 mg/kg),with 20 rats in each group.Rats in the model group,andrographolide group,benazepril group were injected with cationized bovine serum albumin through the tail vein to replicate the MN rat model.The andrographolide group and benazepril group were given intragastric administration once a day for four consecutive weeks.The normal group and model group were given 0.9%sodium chloride solution by gavage once a day for four consecutive weeks.The renal function indicators were detected by biochemical analysis method.Histopathological examination of renal tissue was performed by Hematoxylin-Eosin staining and Masson staining,and ultrastructural changes of renal tissue were observed by transmission electron microscopy(TEM).The contents of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),intercellular adhesion molecule-1(ICAM-1)were detected by enzyme-linked immunosorbent assay(ELISA)method,the expression of proteins were detected by Western blot.RESULTS:Compared with the model group,the renal tissue lesions and ultrastructural lesions in the andrographolide group and benazepril group decreased significantly,and the effect of the andrographolide group was more significant;the 24 h urine protein quantification and creatinine(SCr)levels decreased significantly;the contents of TNF-α,IL-6 and ICAM-1 decreased significantly;the expressions of Toll-like receptor 4(TLR4),nuclear factorκB(NF-κB),transforming growth factorβ1(TGF-β1),phosphorylated Smad2 and phosphorylated Smad3,collagen typeⅠand typeⅢdecreased significantly,and the differences were statistically significant(P<0.01).The above indicators in the andrographolide group were significantly better than those in the benazepril group,with statistically significant differenc
作者
周靖
郭洋洋
陆春红
黄金杰
王丹
ZHOU Jing;GUO Yangyang;LU Chunhong;HUANG Jinjie;WANG Dan(Dept.of Nephrology,Kailuan General Hospital,Hebei Tangshan 063000,China;Dept.of Internal Medicine,the Fourth People’s Hospital of Langfang,Hebei Langfang 065700,China)
出处
《中国医院用药评价与分析》
2022年第9期1075-1080,共6页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
河北省医学科学研究课题计划项目(No.20201370)
河北省唐山市科学技术研究与发展计划项目(No.19130237C)。
