摘要
目的观察红芪多糖(HPS)对糖尿病肾病db/db小鼠NOD样受体蛋白3(NLRP3)/胱天蛋白酶-1(Caspase-1)信号通路的影响。方法将50只db/db小鼠按体质量随机分为模型组、阳性对照组和低、中、高剂量实验组,每组10只。另取10只db/m小鼠作为正常组。正常组和模型组给予等量0.9%NaCl,低、中、高剂量实验组,分别给予50、100和200 mg·kg^(-1)·d^(-1)HPS悬溶液灌胃,阳性对照组给予22.75 mg·kg^(-1)·d^(-1)厄贝沙坦悬溶液,各组小鼠每日灌胃1次,连续给药12周。用苏木精-伊红(HE)和马松(Masson)染色法检测肾组织病理形态及纤维化情况;用蛋白质印迹法和实时荧光定量聚合酶链反应法检测小鼠肾中NLRP3、Caspase-1、核因子-κB p65(NF-κB p65)蛋白及mRNA表达情况。结果模型组与正常组比较,小鼠肾小球基底膜增厚,肾小囊部分粘连,间质区有炎症细胞浸润,系膜区纤维化增生,胶原纤维沉积呈絮团状,各剂量实验组治疗后在不同程度上减轻基底膜增厚、肾小囊粘连及炎性细胞浸润情况,减轻系膜区增生及胶原纤维沉积。正常组、模型组和低、中、高剂量实验组及阳性对照组的NLRP3蛋白表达水平分别为0.44±0.08、1.12±0.03、1.05±0.13、0.75±0.10、0.48±0.11和0.51±0.15;Caspase-1蛋白表达水平分别为0.40±0.03、1.17±0.03、0.93±0.15、0.74±0.06、0.47±0.01和0.44±0.03;NF-κB p65蛋白表达水平分别为0.42±0.11、1.08±0.03、0.92±0.12、0.84±0.07、0.71±0.13和0.55±0.09;肾组织中NLRP3 mRNA表达水平分别为1.00±0.00、2.98±0.43、2.52±0.42、1.66±0.20、1.52±0.32和2.02±0.42;Caspase-1 mRNA表达水平分别为1.00±0.00、3.05±0.25、2.75±0.40、1.85±0.18、1.60±0.01和2.10±0.20;NF-κB p65 mRNA表达水平分别为1.00±0.00、3.21±0.07、3.10±0.32、2.21±0.16、2.00±0.14和2.37±0.49。模型组上述指标与正常组比较,差异均有统计学意义(均P<0.01);中、高剂量实验组及阳性对照组上述指标与模型组比较,差�
Objective To investigate the effect of Hedysari polysaccharide(HPS)on NOD-like receptor protein 3/cysteinyl aspartate specific proteinase-1 signaling pathway in diabetic nephropathy db/db mice.Methods According to body weight,50 db/db mic e were randomly divided into model group,experimental-L,-M,-H groups and positive control group,with 10 mice in each group.Another 10 db/m mice were selected as the normal group.Normal group and model group were given equal doses of 0.9%NaCl,the experimental group were given 50,100 and 200 mg·kg^(-1)·d^(-1) HPS suspension solution by gavage,respectively,and the positive control group were given 22.75 mg·kg^(-1)·d^(-1) irbesartan suspension solution by gavage once a day.The drug was administered continuously for 12 weeks.Hematoxylin-eosin(HE)and Masson staining were used to detect the pathological morphology and fibrosis of kidney tissue;the protein and mRNA expressions of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase-1(Caspase-1),nuclear factor-κB p65(NF-κB p65)in the kidneys of mice in each group were detected by Western blot and Real-time quantitative polymerase chain reaction.Results Compared with the normal group,the glomerular basement membrane of mice in the model group was thickened,the renal capsule was partially adherent,there was obvious inflammatory cell infiltration,fibrosis and hyperplasia in the mesangial region,and the collagen fiber deposition was flocculated.After treatment with different doses of HPS,the basement membrane thickening,the renal capsule adhesion and inflammatory cell infiltration were alleviated to varying degrees.Reduce mesangial hyperplasia and collagen fiber deposition.The expression levels of NLRP3 protein were 0.44±0.08,1.12±0.03,1.05±0.13,0.75±0.10,0.48±0.11 and 0.51±0.15 in the normal group,model group,experimental-L,-M,-H groups and positive control group,respectively;the expression levels of Caspase-1 protein were 0.40±0.03,1.17±0.03,0.93±0.15,0.74±0.06,0.47±0.01 and 0.44±0.03,respectively;th
作者
姜晓雪
金智生
陈彦旭
张钦媛
张博玲
伏瑶琴
金彩云
JIANG Xiao-xue;JIN Zhi-sheng;CHEN Yan-xu;ZHANG Qin-yuan;ZHANG Bo-ling;FU Yao-qin;JIN Cai-yun(Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第21期3125-3129,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(82060854)
甘肃省优秀博士生基金项目(23JRRA1221)
研究生创新基金资助项目(2022CX02)。
