精氨酸酶Ⅱ在2型糖尿病肾病大鼠肾组织中的表达及作用  

Expression and role of ArginaseⅡin the kidney tissues of rats with type 2 diabetic nephropathy

作　　者：李秀 张海英 江玉波 王少清 莫梓沂 薛世圆 刘畅 LI Xiu;ZHANG Hai-ying;JIANG Yu-bo;WANG Shao-qing;MO Zi-yi;XUE Shi-yuan;LIU Chang(School of Basic Medicine,Chengdu Medical College,Chengdu Sichuan 610500,China;Department of Endocrinology and Metabolism,Pidu District People's Hospital of Chengdu,Chengdu Sichuan 611730,China;Department of Nephrology,Second Affiliated Hospital of Chengdu Medical College,Chengdu Sichuan 610057,China;School of Pharmacy,Chengdu Medical College,Chengdu Sichuan 610500,China;School of Clinical Medicine,Chengdu Medical College,Chengdu Sichuan 610500,China)

机构地区：[1]成都医学院基础医学院,四川成都610500 [2]成都市郫都区人民医院内分泌代谢科,四川成都611730 [3]成都医学院第二附属医院肾内科,四川成都610057 [4]成都医学院药学院,四川成都610500 [5]成都医学院临床医学院,四川成都610500

出　　处：《局解手术学杂志》2025年第3期205-211,共7页Journal of Regional Anatomy and Operative Surgery

基　　金：四川省自然科学基金(2022NSFSC0759);发育与再生四川省重点实验室开放课题(23LHPDZYB16,24LHFYSZ1-47);四川省大学生创新创业训练计划(S202313705059);成都医学院科研基金项目(CYZYB20-15);成都医学院-成都医学院第一附属中医医院新都区中医医院临床科学研究基金项目(2022LHZYYB-21);成都医学院-成都医学院第二附属医院核工业416医院临床科学研究基金项目(2022LHFSZYB-15)。

摘　　要：目的探讨精氨酸酶Ⅱ(ArgⅡ)在糖尿病肾病(DN)大鼠肾组织中的表达及其在DN发生过程中的作用。方法10只雄性SD大鼠随机分为对照组和模型组,每组5只。采用高糖高脂饲料饲养和腹腔注射小剂量链脲佐菌素(45 mg/kg)制作大鼠DN模型,继续饲养11周后处死。测定大鼠体质量和血、尿生化指标;取右肾称重并进行病理学检查,观察肾组织病理学变化和ArgⅡ、CD68^(+)蛋白表达,免疫荧光双染色法观察ArgⅡ与肾巨噬细胞活化标志因子CD68^(+)的分布和表达情况;Western blot检测肾组织中ArgⅡ、NF-κB、TNF-α、IL-6蛋白表达情况。结果与对照组相比,模型组肾质量/体质量、24 h尿量、24 h尿蛋白、空腹血糖、尿素氮和胰岛素水平均明显增高(P<0.05)。肾组织病理学结果显示:模型组大鼠肾小球系膜细胞坏死,血管扩张,肾小管上皮细胞脂肪变性、淤血。与对照组比较,模型组大鼠肾组织ArgⅡ、CD68^(+)、NF-κB、TNF-α、IL-6蛋白表达均明显升高(P<0.05)。免疫荧光双染色显示,ArgⅡ和CD68^(+)共表达于肾组织中,且模型组大鼠ArgⅡ、CD68^(+)荧光强度强于对照组(P<0.01)。结论ArgⅡ在DN中表达增高,其可能参与了DN炎性病变的发生。Objective To investigate the expression of arginaseⅡ(ArgⅡ)in kidney tissue of rats with diabetic nephropathy(DN)and its significance in the development of DN.Methods A total of 10 male SD rats were randomly divided into the control group and the model group,with 5 rats in each group.An rat model of DN was developed by feeding with high-sugar and high-fat diet combined with intraperitoneal injection of low-dose streptozotocin(45 mg/kg),and they were sacrificed after 11 weeks of continued feeding.The body weight,and biochemical indexes of blood and urine of rats were determined.The right kidney was weighed and histopathological examination was performed.The pathological changes of kidney tissues and protein expression of ArgⅡand CD68^(+)were observed,and the immunofluorescence double staining was used to observe the distribution and expression of ArgⅡand a marker of renal macrophage activation CD68^(+);the protein expression of ArgⅡ,NF-κB,TNF-αand IL-6 in kidney tissues was determined by Western blot.Results Compared with the control group,the ratio of kidney weight to body weight,24-hour urine volume,24-hour urine protein,fasting blood glucose,urea nitrogen and insulin level in the model group were significantly increased(P<0.05).The renal histopathology showed that the mesangial cells of the renal glomerular were necrotic with vascular dilatation,and the renal tubular epithelial cells were steatosis and congestion.Compared with the control group,the protein expression of ArgⅡ,CD68^(+),NF-κB,TNF-αand IL-6 in the kidney tissues of the model group were significantly increased(P<0.05).Immunofluorescence double staining demonstrated the co-expression of ArgⅡand CD68^(+)in renal tissue,and the fluorescence intensities of both ArgⅡand CD68^(+)in the model group were significantly stronger than those in the control group(P<0.01).Conclusion The expression of ArgⅡis increased in DN,which may be participated in the occurrence of inflammatory lesions in DN.

关 键 词：精氨酸酶Ⅱ 糖尿病肾病 肾巨噬细胞 免疫炎症 

分 类 号：R364.5[医药卫生—病理学]