泽泻多糖激活PPAR-γ/LXR-α/ABCG1信号通路发挥对糖尿病肾病大鼠的保护作用  

Protective effect of Alisma orientalis polysaccharides on diabetes nephropathy rats by activating PPAR-γ/LXR-α/ABCG1 signaling pathway

作　　者：董莹莹 张秀媛 王洁 DONG Yingying;ZHANG Xiuyuan;WANG Jie(Department of Endocrinology,Shunyi Hospital,Beijing Traditional Chinese Medicine Hospital,Beijing 101300,China)

机构地区：[1]北京中医医院顺义医院内分泌科,北京101300

出　　处：《药物评价研究》2023年第7期1480-1487,共8页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81904190)。

摘　　要：目的 探究泽泻多糖对糖尿病大鼠肾损伤的改善作用。方法 SPF级SD雄性大鼠随机分为对照组,模型组,吡格列酮[过氧化物酶体增殖物激活受体γ(PPAR-γ)激活剂,20 mg·kg^(-1)]组,泽泻多糖低、中、高剂量(100、200、400 mg·kg^(-1))组和泽泻多糖(400 mg·kg^(-1))+GW9662 (PPAR-γ抑制剂,10 mg·kg^(-1))组,除对照组外均采用高糖高脂+链脲佐菌素(STZ)柠檬酸钠缓冲液法制备糖尿病肾病(DN)大鼠模型,造模后各组ig给药,每天1次,连续6周。血糖仪测定大鼠空腹血糖(FBG)水平;全自动生化分析仪检测大鼠血清肌酐、尿酸、尿素氮水平,检测24 h尿蛋白及尿肌酐,计算内生肌酐清除率(Ccr);处死大鼠,计算大鼠肾脏指数;HE染色观察大鼠右侧肾脏组织病理学变化;Western blotting法检测肾脏组织PPAR-γ/肝X受体-α(LXR-α)/ATP结合盒转运蛋白G1(ABCG1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)蛋白水平。结果 与对照组比较,模型组大鼠毛色枯黄,体质量显著减轻(P<0.05);肾小球细胞空泡化、肾小球基底膜增厚;肾脏指数、FBG、24 h尿蛋白、尿酸、尿素氮、TNF-α和IL-1β蛋白水平显著升高(P<0.05),Ccr和PPAR-γ、LXR-α、ABCG1蛋白水平显著降低(P<0.05);与模型组比较,吡格列酮组和中、高剂量泽泻多糖组大鼠毛色及饮食、饮水逐渐恢复,体质量显著增加(P<0.05);肾损伤程度减轻;FBG、24 h尿蛋白、尿酸、TNF-α和IL-1β蛋白水平显著降低(P<0.05),Ccr及PPAR-γ、LXR-α、ABCG1蛋白水平显著升高(P<0.05);泽泻多糖高剂量组肾脏指数显著降低(P<0.05)。高剂量泽泻多糖组与吡格列酮组各指标差异比较无统计学意义,GW9662可逆转高剂量泽泻多糖对大鼠肾脏功能的保护作用。结论 泽泻多糖可能通过激活PPAR-γ/LXR-α/ABCG1通路保护DN大鼠肾脏。Objective To explore the ameliorative effect of Alisma orientalis polysaccharide(AOP) on renal injury in diabetes rats.Methods Fifty SPF male SD rats were randomly divided into control group,model group and pioglitazone group(PPAR-γ activator,20 mg·kg^(-1)),AOP low,medium and high dose(100,200,and 400 mg·kg^(-1)) group,AOP high dose(400 mg·kg^(-1)) + GW9662(PPAR-γ inhibitor,10 mg·kg^(-1)) group,except the control group,DM rat models were made by high glucose and high fat + streptozotocin(STZ) sodium citrate buffer method.After modeling,each group was administered ig once a day for six consecutive weeks.After administration,serum fasting blood glucose(FBG),serum creatinine,uric acid and urea nitrogen were measured by fully automatic biochemical analyzer.The levels of 24-hour urinary protein and urinary creatinine were measured,and the endogenous creatinine clearance rate(CCR) was calculated.The rats were sacrificed and the renal index was calculated.The histopathological changes of the right kidney were observed by HE staining.Renal peroxisome proliferator activated receptor γ(PPAR-γ)/liver X receptor-α(LXR-α)/ATP binding cassette transporter G1(ABCG1),TNF-α,IL-1β protein level was detected by Western blotting.Results Compared with the control group,the model group had withered and yellow hair,reduced body weight(P<0.05),vacuolization of glomerular cells,thickening of glomerular basement membrane,renal index,FBG,24-h urinary protein,uric acid,urea nitrogen and the protein level of TNF-α and IL-1β increased(P<0.05),CCR and the protein level of PPAR-γ,LXR-α,ABCG1 decreased(P<0.05).Compared with model group,the hair color,diet and drinking water of pioglitazone group,medium and high dose AOP group gradually recovered,the body weight increased(P<0.05),the degree of renal injury decreased,FBG,24-h urinary protein,uric acid and the protein level of TNF-α and IL-1β decreased(P<0.05),CCR and PPAR-γ,LXR-α,and ABCG1 protein level increased(P<0.05),the kidney index of the high-dose group of AOP significan

关 键 词：糖尿病肾病 泽泻多糖 过氧化物酶体增殖物激活受体γ 肝X受体-α ATP结合盒转运蛋白G1 

分 类 号：R285.5[医药卫生—中药学] R587.1[医药卫生—中医学]