达格列净预处理对对比剂肾病大鼠炎症反应及肾小管上皮细胞凋亡的影响  

Effect of dapagliflozin pretreatment on inflammatory responses and apoptosis of renal tubular epithelial cells in rats with contrast-induced nephropathy

作　　者：李依阳[1] 邝日禹[1] 张涛[2] 苏晓琳[1] 雷玲艳 覃凯[1] 谭妍妍 LI Yiyang;KUANG Riyu;ZHANG Tao;SU Xiaolin;LEI Lingyan;QIN Kai;TAN Yanyan(Department of Cardiovascular Medicine,Minzu Hospital of Guangxi Zhuang Autonomous Region,Nanning 530001,Guangxi,China;Department of Neurological Medicine,the No.923 Hospital of the Joint Logistic Support Force of the Chinese People′s Liberation Army,Nanning 530021,Guangxi,China)

机构地区：[1]广西壮族自治区民族医院心血管内科,广西南宁市530001 [2]中国人民解放军联勤保障部队第923医院神经内科,广西南宁市530021

出　　处：《广西医学》2023年第8期928-932,共5页Guangxi Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹经费科研课题(Z20210583)。

摘　　要：目的探讨达格列净预处理对对比剂肾病(CIN)大鼠炎症反应及肾小管上皮细胞凋亡的影响。方法将18只SD大鼠随机分为正常组、模型组、达格列净组。取模型组、达格列净组大鼠,采用尾静脉注射吲哚美辛、左旋硝基精氨酸甲酯、碘海醇注射液制备CIN大鼠模型。造模前2 h,给予达格列净组大鼠灌胃达格列净,给予正常组、模型组大鼠灌胃生理盐水。造模24 h后,检测各组大鼠血清白细胞介素1β(IL-1β)含量,以及肾脏组织的髓过氧化物酶(MPO)含量、肾小管上皮细胞凋亡情况、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)表达水平、Caspase-3及cleaved Caspase-3蛋白表达水平。结果正常组、达格列净组、模型组大鼠血清IL-1β含量及肾脏组织的肾小管上皮细胞凋亡率、NLRP3表达水平、cleaved Caspase-3蛋白表达水平与Caspase-3蛋白表达水平的比值均依次升高(均P<0.05)。3组大鼠肾脏组织MPO含量差异无统计学意义(P>0.05)。结论达格列净预处理可能通过抑制NLRP3炎性小体通路的活性和炎症因子的表达来减轻CIN大鼠的炎症反应,并通过抑制Caspase-3活化来减少肾小管上皮细胞凋亡,进而发挥肾脏保护作用。Objective To investigate the effect of dapagliflozin pretreatment on inflammatory responses and apoptosis of renal tubular epithelial cells in rats with contrast-induced nephropathy(CIN).Methods A total of 18 SD rats were randomly assigned to normal group,model group,or dapagliflozin group.Rats in the model and dapagliflozin groups received caudal intravenous injection of indomethacin,L-nitroarginine methyl ester,and Iohexol Injection for preparing CIN rat model.Before 2 hours of modeling,rats in the dapagliflozin group received intragastric administration of dapagliflozin,and rats in the normal and model groups received intragastric administration of normal saline.After 24 hours of modeling,the contents of serum interleukin 1β(IL-1β)and myeloperoxidase(MPO)in renal tissues,and apoptosis of renal tubular epithelial cells in renal tissues,as well as expressions of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase-3 and cleaved Caspase-3 proteins in renal tissues were detected in rats of various groups.Results Serum IL-1βcontent,and apoptosis rate of renal tubular epithelial cells,NLRP3 expression,and cleaved Caspase-3 protein expression to Caspase-3 protein expression ratio in renal tissues were successively elevated in the normal,dapagliflozin,and model groups(all P<0.05).No statistically significant difference in MPO content in rats′renal tissues was found between the three groups(P>0.05).Conclusion Dapagliflozin pretreatment may reduce CIN rats′inflammatory responses by inhibiting the activity of NLRP3 inflammasome pathway and inflammatory factors expressions,and reduce apoptosis of renal tubular epithelial cells by inhibiting the activation of Caspase-3,thereby exerting a renoprotective effect.

关 键 词：对比剂肾病 达格列净 核苷酸结合寡聚化结构域样受体蛋白3 炎性小体 炎症因子 细胞凋亡 CASPASE-3 

分 类 号：R692.9[医药卫生—泌尿科学]