关黄柏多糖对大鼠痛风性肾病的改善作用及机制研究  

Improvement effect of Phellodendron amurense polysaccharides on gouty nephropathy in rats and its mechanism

作　　者：马永哲 王宇亮[1] 张凯 赵宏[1,2] 沈宇 邱洪斌[3] 王朝兴[1] 孙诗晴[1] 姜振旭 宋明明 张宇 MA Yongzhe;WANG Yuliang;ZHANG Kai;ZHAO Hong;SHEN Yu;QIU Hongbin;WANG Chaoxing;SUN Shiqing;JIANG Zhenxu;SONG Mingming;ZHANG Yu(College of Pharmacy,Jiamusi University,Heilongjiang Jiamusi 154007,China;Heilongjiang Provincial Key Laboratory of New Drug Discovery and Efficacy Toxicology Evaluation,Heilongjiang Jiamusi 154007,China;School of Public Health,Jiamusi University,Heilongjiang Jiamusi 154007,China)

机构地区：[1]佳木斯大学药学院,黑龙江佳木斯154007 [2]黑龙江省新药创制与药效毒理评价重点实验室,黑龙江佳木斯154007 [3]佳木斯大学公共卫生学院,黑龙江佳木斯154007

出　　处：《中国药房》2024年第5期555-559,共5页China Pharmacy

基　　金：黑龙江省自然科学基金优秀青年项目(No.YQ2023H001);黑龙江省教育厅科技创新团队建设计划(No.2021-KYYEF-0638);黑龙江省省属高等学校基本科研项目(No.2022-KYYWF-0612);黑龙江省北药与功能食品“双一流”特色学科项目(No.HLJTSXK-2022-03)。

摘　　要：目的研究关黄柏多糖(PAP)对大鼠痛风性肾病(GN)的改善作用,并通过丝裂原激活蛋白激酶p38(p38 MAPK)/核因子κB(NF-κB)/肿瘤坏死因子α(TNF-α)信号通路初步探讨其作用机制。方法将60只大鼠按体重分层后随机分为正常组(水)、模型组(水)、别嘌醇组(阳性对照,20 mg/kg)和PAP高、中、低剂量组(100、50、25 mg/kg,以生药量计),每组10只。除正常组外,其余各组大鼠均采取1500 mg/kg氧嗪酸钾和100 mg/kg腺嘌呤联合灌胃14 d构建GN模型。造模成功后,各组大鼠灌胃相应药物/水,每天1次,连续28 d。末次给药后,检测大鼠肾功能相关生化指标[尿酸、肌酐(Cr)、血尿素氮(BUN)、黄嘌呤氧化酶(XOD)],观察大鼠肾组织病理形态学变化,检测大鼠肾组织中单核细胞趋化蛋白1(MCP-1)、TNF-α、白细胞介素6(IL-6)蛋白表达水平和p38MAPK、NF-κB p65蛋白的磷酸化水平。结果与正常组比较,模型组大鼠肾小管扩张,肾小球结构损坏,并伴有炎症浸润与纤维化;尿酸、Cr、BUN、XOD含量以及MCP-1、TNF-α、IL-6蛋白表达水平和p38 MAPK、NF-κB p65蛋白的磷酸化水平均显著升高(P<0.05或P<0.01)。与模型组比较,PAP各剂量组大鼠的肾组织病理症状均有不同程度改善;PAP高、中剂量组大鼠尿酸、Cr、BUN、XOD含量以及MCP-1、TNF-α、IL-6蛋白表达水平和p38 MAPK、NF-κB p65蛋白的磷酸化水平均显著降低(P<0.05或P<0.01)。结论PAP具有抗GN的作用,其机制可能与抑制p38 MAPK/NF-κB/TNF-α信号通路的激活有关。OBJECTIVE To study the effects of Phellodendron amurense polysaccharides(PAP)on improving gouty nephropathy(GN)in rats,and to investigate its mechanism primarily by interfering the p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor-κB(NF-κB)/tumor necrosis factor-α(TNF-α).METHODS Sixty rats were randomly divided into normal group(water),model group(water),allopurinol group(positive control,20 mg/kg),PAP high-dose,medium-dose and low-dose groups(100,50,25 mg/kg,by raw material)after being stratified by body weight,with 10 rats in each group.Except for the normal group,the other groups were induced to construct GN model by giving 1500 mg/kg potassium oxazinate and 100 mg/kg adenine intragastrically for 14 days.After modeling,the rats in each group were given relevant medicine/water intragastrically,once a day,for consecutive 28 days.After the last medication,the levels of biochemical parameters related to renal function[uric acid,creatinine(Cr),blood urea nitrogen(BUN),xanthine oxidase(XOD)]were detected in rats,and the histopathological changes in the rat kidney were observed.The protein expressions of monocyte chemoattractant protein-1(MCP-1),TNF-αand interleukin-6(IL-6)as well as the phosphorylation levels of p38 MAPK and NF-κB p65 protein were determined in renal tissue of rats.RESULTS Compared with the normal group,the model group suffered from the dilatation of renal tubules,structural damage to glomeruli,accompanied by inflammatory infiltration and fibrosis;the contents of uric acid,Cr,BUN and XOD,the protein expressions of MCP-1,TNF-αand IL-6 and the phosphorylation levels of p38 MAPK and NF-κB p65 protein were all increased significantly(P<0.05 or P<0.01).Compared with the model group,the pathological symptoms of renal tissue in rats had been improved to varying degrees in different dose groups of PAP;the contents of uric acid,Cr,BUN and XOD,protein expressions of MCP-1,TNF-αand IL-6,the phosphorylation levels of p38 MAPK and NF-κB p65 protein in PAP high-dose and PAP medium-dose group

关 键 词：关黄柏多糖 痛风性肾病 炎症因子 丝裂原激活蛋白激酶p38 核因子ΚB 肿瘤坏死因子Α 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]