摘要
目的研究槲皮素对SLE小鼠肾保护作用并探讨其对TGF-β1、单核细胞趋化蛋白-1(MCP-1)的影响。方法将30只BALB/c雌性小鼠依据信封法随机分为对照组、模型组和药物组,每组各10只。采用腹腔注射降值烷(pristane)法构建SLE小鼠模型,药物组给予槲皮素治疗,对照组和模型组均给予同等剂量0.9%氯化钠注射液治疗。比较各组小鼠的肾功能指标、自身抗体水平。采用HE染色法观察各组肾组织病理形态改变,使用蛋白质印迹法和实时荧光定量反转录聚合酶链反应(qRT-PCR)技术测定TGF-β1、MCP-1的表达情况。采用单因素方差分析法对肾功能指标、自身抗体水平、TGF-β1、MCP-1的表达量进行统计学分析。结果模型组和药物组小鼠尿素氮、血肌酐、尿蛋白定量(24h)、肾脏肥大指数、ANA、抗dsDNA抗体、抗小核糖核蛋白(抗snRNP)/Sm抗体均高于对照组;与模型组比较,药物组小鼠血尿素氮、血肌酐、尿蛋白定量(24h)、肾脏肥大指数、ANA、抗dsDNA抗体、抗snRNP/Sm抗体分别为[(11.3±1.1)mmol/L、(45±4)μmol/L、(25.7±2.6)mg/24h、(4.3±0.4)×10^-3、(30.3±3.1)ng/L、(472±48)μmol/L和(17.6±1.8)ng/L]均降低(q=10.678,6.698,14.948,14.412,9.226,4.691,8.226,P<0.01)。模型组小鼠肾小球评分、肾小管间质评分和肾小管评分均高于对照组(q=43.121,95.781,40.586,P<0.01),药物组肾小球评分、肾小管间质评分和肾小管评分均低于模型组(q=10.953,49.537,20.439,P<0.01)。HE染色显示对照组肾脏形态结构正常;模型组小鼠肾小球体积增大,肾间质、肾小管周围炎症细胞浸润;药物组病理改变较模型组明显减轻。与对照组小鼠比较,模型组和药物组小鼠的TGF-β1、MCP-1蛋白和mRNA表达水平均升高;与模型组小鼠相比,药物组小鼠TGF-β1、MCP-1蛋白和mRNA表达水平降低。结论槲皮素可改善SLE小鼠肾功能,其可能的机制是通过下调TGF-β1、MCP-1的表达。
Objective To study the protective effect of quercetin on the kidney of mice with systemic lupus erythematosus (SLE) and to explore its effect on transforming growth factor (TGF)-β1 and monocyte chemoattractant protein-1 (MCP-1). Methods Thirty BALB/c female mice were randomly divided into control group, model group and drug group according to the envelope method, with 10 mice in each group. A mouse model of SLE was established by intra-peritoneal injection of pristane method. The drug group was given quercetin treatment, and the control group and the model group were given the same dose of normal saline. The renal function index and autoanti-body level in each group of mice were compared. The pathological changes of renal tissues were observed by HE staining. The expressions of TGF-β1 and MCP-1 were determined by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR). The renal function index, autoantibody level, TGF-β1, and MCP-1 expression were statistically analyzed by analysis of one-way analysis of variance (ANOVA). Results The levels of blood urea nitrogen (BUN), serum creatinine (Scr), 24 h urine protein, kidney hypertrophy index, antinuclear antibody (ANA) antibody, anti-dsDNA antibody and anti-snRNP/Sm in the model group and the drug group were higher than those in the control group. Compared with the model group, the levels of BUN, Scr, 24 h urine protein, kidney hypertrophy index, ANA antibody, anti-dsDNA antibody, anti-snRNP/Sm in the drug group were(11.3±1.1) mmol/L,(45±4)μmol/L,(25.7±2.6) mg/24 h,(4.3±0.4)×10^-3,(30.3±3.1) ng/L,(472±48)μmol/L and (17.6±1.8) ng/L, which were decreased (q=10.678, 6.698, 14.948, 14.412, 9.226, 4.691, 8.226, P<0.01). The glomerular score, tubulointerstitial score and tubulointer-stitial score of the model group were higher than those of the control group. The glomerular score, tubulointer-stitial score and tubular score of the drug group were lower than those of the model group (q=10.935, 49.537, 20.439, P<0.01). HE staining showed that the kidney structure of the control group was no obvious damage. In the model group, the glomerular volume of the mice increased, and the inflammatory cells in the renal interstitial and renal tubules infiltrated. The pathological changes in the drug group were significantly reduced compared with the model group. Compared with the control group, the expression levels of TGF-β1, MCP-1 protein and mRNA in the model group and the drug group were significantly increased. Compared with the model group, TGF-β1 and MCP-1 protein and mRNA expression levels the mice in the drug group were significantly reduced. Conclusion Quercetin can improve renal function in mice with SLE by down-regulating the expression of TGF-beta 1 and MCP-1.
作者
户庆峰
王学珍
魏新平
Hu Qingfeng;Wang Xuezhen;Wei Xinping(Department of Nephrology and Rheumatology,the First People's Hospital of Shangqiu,Henan 476100,China)
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2019年第5期309-313,I0003,共6页
Chinese Journal of Rheumatology
关键词
槲皮素
红斑狼疮
系统性
肾脏
转化生长因子β1
单核细胞趋化蛋白-1
Quercetin
Lupus erythematosus, systemic
Kidney
Transforming growth factor-β1
Monocyte chemoattractant protein-1
