白杨素通过抑制IRE1α/TXNIP/NLRP3通路减轻糖尿病大鼠的肾组织损伤  

Chrysin attenuating renal tissue damage in rats with diabetes mellitus by inhibiting IRE1α/TXNIP/NLRP3 pathway

作　　者：王芳 王卫军 张文涛 张涛 田晓慧 WANG Fang;WANG Wei-jun;ZHANG Wen-tao;ZHANG Tao;TIAN Xiao-hui(Department of Hematology and Endocrinology,Xianyang Hospital of Yan'an University,Xianyang Shaanxi 712000,China;Department of Nephrology,Xianyang Hospital of Yan'an University,Xianyang Shaanxi 712000,China;Department of Cadre Health Care,Xianyang First People's Hospital,Xianyang Shaanxi 712000,China)

机构地区：[1]延安大学咸阳医院血液内分泌科,陕西咸阳712000 [2]延安大学咸阳医院肾病科,陕西咸阳712000 [3]咸阳市第一人民医院干部保健病区,陕西咸阳712000

出　　处：《局解手术学杂志》2023年第11期979-984,共6页Journal of Regional Anatomy and Operative Surgery

基　　金：陕西省卫生健康科研基金项目(2021D015)。

摘　　要：目的 探讨白杨素(CHR)通过抑制肌醇需求酶1α(IRE1α)/硫氧还蛋白结合蛋白(TXNIP)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路减轻糖尿病大鼠肾组织损伤的机制。方法 将健康SPF级SD大鼠随机分为对照组、模型组、CHR组、CHR+溶剂对照组、CHR+IRE1α组,每组8只。除对照组外,其余各组高脂高糖饲料饲养联合30 mg/kg链脲佐菌素(STZ)注射构建糖尿病模型,CHR组、CHR+溶剂对照组、CHR+IRE1α组采用100 mg·kg^(-1)·d^(-1) CHR连续灌胃3周,CHR+溶剂对照组、CHR+IRE1α组同时分别腹腔注射1 m L磷酸缓冲液、1×10^(9) PFU/m L Ad-IRE1α病毒悬液;对照组、模型组腹腔注射等量生理盐水。观察大鼠一般情况并称重;检测空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;全自动生化分析仪检测大鼠血清肌酐(s Cr)、血尿素氮(BUN)水平;苏木精-伊红染色观察肾组织形态;蛋白免疫印迹法检测肾组织中IRE1α、TXNIP、NLRP3、caspase-1、白介素-1β(IL-1β)蛋白表达情况。结果 模型组大鼠出现多饮、多尿、多食、消瘦情况,精神状态欠佳,肾小球肥大、基质增厚,肾小球毛细血管间有结节状粉红色玻璃样物,肾小管内皮气球样变,部分细胞出现核固缩现象;CHR组、CHR+溶剂对照组较模型组身体和精神状态有所改善,肾小球、肾小管病理现象缓解;CHR+IRE1α组相较CHR组肾小球肥大、基质变厚加重,肾小管出现病变。与对照组相比,模型组血液中FPG、TG、TC、LDL-C、s Cr、BUN水平及肾脏组织中IRE1α、TXNIP、caspase-1、NLRP3、IL-1β蛋白水平升高(P<0.05),体质量减轻(P<0.05),HDL-C水平降低(P<0.05);与模型组相比,CHR组血液中FPG、TG、TC、LDL-C、s Cr、BUN水平及肾组织中IRE1α、TXNIP、caspase-1、NLRP3、IL-1β蛋白水平降低(P<0.05),体质量增加(P<0.05),HDL-C水平升高(P<0.05);与CHR组相比,CHR+IRE1α组血液中FPG、TG�Objective To investigate the mechanism of chrysin (CHR) attenuating renal tissue damage in rats with diabetes mellitus by inhibiting inositol-requiring enzyme 1alpha (IRE1α)/thioredoxin-interacting protein (TXNIP)/nucleotide binding oligomerization domainlike receptor protein 3 (NLRP3) pathway.Methods Healthy SPF-grade SD rats were randomly divided into the control group,model group,CHR group,CHR+solvent control group,and CHR+IRE1αgroup,with 8 rats in each group.Except for the control group,other groups were fed with high-fat and high-sugar diet combined with 30 mg/kg of streptozotocin (STZ) injection to build the model of diabetes mellitus.The CHR group,CHR+solvent control group and CHR+IRE1αgroup were given enteral nutrition by 100 mg·kg^(-1)·d^(-1) of CHR for 3 weeks,the CHR+solvent control group and the CHR+IRE1αgroup were intraperitoneally injected with 1 m L of phosphate buffer solution and 1×10^(9) PFU/m L of Ad-IRE1αvirus suspension,respectively,and the control group and the model group were intraperitoneally injected with an equal volume of normal saline.The rats were observed for general condition and weighed;the levels of fasting blood glucose (FPG),total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C)and high-density lipoprotein cholesterol (HDL-C) were detected;the levels of serum creatinine (s Cr) and blood urea nitrogen (BUN) were detected by automatic biochemical analyzer;the morphology of renal tissue was observed by hematoxylin-eosin staining;the protein expressions of IRE1α,TXNIP,NLRP3,caspase-1 and interleukin-1β(IL-1β)in renal tissue were determined by Western blot.Results The rats in the model group showed polydipsia,polyuria,polyphagia,weight loss and poor mental state,the glomeruli was hypertrophied with the matrix thickening and nodular pink glass-like materials between the glomerular capillaries,the renal tubular endothelium had ballooning changes,with nuclear pyknosis in some cells.The physical and mental states of the CHR group and the CHR+solv

关 键 词：白杨素 肌醇需求酶1α/硫氧还蛋白结合蛋白/核苷酸结合寡聚化结构域样受体蛋白3通路 糖尿病 大鼠 肾组织损伤 

分 类 号：R285.5[医药卫生—中药学]