琥珀酸受体1加重肾脏缺血再灌注损伤的作用研究  

Role of succinate receptor 1 in exacerbation of kidney ischemia-reperfusion injury

作　　者：彭瑞 杨瑞文[1] 魏澹宁 夏永良[1,2] Rui Peng;Ruiwen Yang;Danning Wei;Yongliang Xia(Health Management Center,the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine,Hangzhou 310003,China;General Medicine Department,the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine,Hangzhou 310003,China)

机构地区：[1]浙江中医药大学附属第一医院健康管理中心,杭州310003 [2]浙江中医药大学附属第一医院全科医学科,杭州310003

出　　处：《中华移植杂志（电子版）》2024年第3期159-164,共6页Chinese Journal of Transplantation(Electronic Edition)

基　　金：浙江省中医药科技计划(2023ZR023)。

摘　　要：目的:探究琥珀酸受体1(SUCNR1)在肾脏缺血再灌注损伤(IRI)中的可能作用及机制。方法:选取40只20~25 g的SPF级C57雄性小鼠分为假手术组、假手术+琥珀酸组、假手术+IgG组、假手术+SUCNR1抗体组、IRI组、IRI+IgG组、IRI+琥珀酸组和IRI+SUCNR1抗体组。IRI模型构建成功后取小鼠血清行肾功能和细胞因子检测,同时取小鼠肾脏组织行病理组织学染色以及SUCNR1 mRNA和蛋白表达分析。组间计量资料比较采用独立样本t检验;多组间比较采用单因素方差分析,组间两两比较采用Bonferroni检验。P<0.05为差异有统计学意义。结果:假手术组和IRI组血清琥珀酸含量分别为(28.74±3.14)和(52.60±4.66)μmol/L,差异有统计学意义(t=-9.494,P<0.05);假手术组与IRI组小鼠肾脏组织SUCNR1 mRNA相对水平分别为(1.00±0.14)和(3.65±1.05),差异有统计学意义(t=-5.567,P<0.05);假手术组与IRI组小鼠肾脏组织SUCNR1蛋白相对表达水平分别为(0.16±0.04)和(0.63±0.06),差异有统计学意义(t=-14.574,P<0.05)。假手术组、假手术+琥珀酸组、IRI组及IRI+琥珀酸组小鼠血清肌酐和尿素氮差异均有统计学意义(F=176.15和131.05,P均<0.05)。与IRI组相比,IRI+琥珀酸组小鼠肾脏组织病理结果示损伤加重。假手术组、假手术+琥珀酸组、IRI组及IRI+琥珀酸组小鼠血清IL-6和TNF-α水平差异均有统计学意义(F=256.25和268.99,P均<0.05)。假手术+IgG组、假手术+SUCNR1抗体组、IRI+IgG组以及IRI+SUCNR1抗体组血清肌酐和尿素氮水平差异均有统计学意义(F=54.13和84.52,P均<0.05)。与IRI+IgG组相比,IRI+SUCNR1抗体组小鼠肾脏组织中肾小管损伤、间质扩张水肿和炎症细胞浸润等均减轻。与IRI+IgG组相比,IRI+SUCNR1抗体组小鼠肾脏组织凋亡水平减轻。假手术组、假手术+SUCNR1抗体组、IRI组以及IRI+SUCNR1抗体组小鼠血清中IL-6和TNF-α差异均有统计学意义(F=123.31和268.144,P均<0.05)。结论:SUCNR1可能通过促进小鼠肾脏�Objective To investigate the possible role and underlying mechanism of succinate receptor 1(SUCNR1)in kidney ischemia-reperfusion injury(IRI).Methods Forty male C57 mice weighing 20-25 g with SPF grade were divided into 8 groups:sham-operated group,sham-operated+succinate group,sham-operated+IgG group,sham-operated+SUCNR1 antibody group,IRI group,IRI+IgG group,IRI+succinate group,and IRI+SUCNR1 antibody group.After the successful establishment of the IRI model,kidney function and cytokines level were measured from the serum,while the mice kidney tissues were obtained for pathological and histological staining as well as SUCNR1 mRNA and protein expression analysis.Measurement data between groups were analyzed by independent Student′s t-test.One-way analysis of variance was used for comparison among multiple groups,and that between groups with P<0.05 denoted statistical significance.Results Serum succinate levels in the sham-operated group and IRI group were(28.74±3.14)and(52.60±4.66)μmol/L,respectively,with statistically significant difference(t=-9.494,P<0.05);the relative levels of SUCNR1 mRNA in the sham-operated group and IRI group were(1.00±0.14)and(3.65±1.05),respectively,with statistically significant difference(t=-5.567,P<0.05);the relative expression levels of SUCNR1 protein in the sham-operated group and IRI group were(0.16±0.04)and(0.63±0.06),respectively,and the difference was statistically significant(t=-14.574,P<0.05).The differences in serum creatinine and urea nitrogen in mice in the sham-operated group,sham-operated+succinate group,IRI group and IRI+succinate group were statistically significant(F=176.15 and 131.05,all P<0.05).Renal tubular injury,interstitial dilatation and edema,and inflammatory cell infiltration were observed in the IRI group compared to the sham-operated group,which were aggravated in IRI+succinate group.The level of apoptosis in the renal tissues of mice in IRI+succinate group was significantly increased compared with that in the IRI group.The differences in serum IL-

关 键 词：肾脏 琥珀酸受体 缺血再灌注损伤 急性肾损伤 

分 类 号：R699.2[医药卫生—泌尿科学]