在线办公
期刊论坛
主 管
中国人民解放军总医院
主 办
解放军总医院医学创新研究部、国家老年疾病临床医学研究中心(解放军总医院)、解放军总医院第六医学中心心血管病医学部
编 辑
中华老年多器官疾病杂志编辑委员会
100853, 北京市复兴路28号
电话:010-66936756
传真:010-66936756
E-mail: zhlndqg@mode301.cn
创刊人 王士雯
主 编 范利
执行主编 陈韵岱
编辑部主任 王雪萍
ISSN 1671-5403
CN 11-4786
创刊时间 2002年
出版周期 月刊
邮发代号 82-408
友情链接
马秀琦,薛君,张莹,武学慧,张雅楠,蔡志杰,闫锐晶.利拉鲁肽对糖尿病肾病大鼠NOD样受体热蛋白结构域相关蛋白3表达的影响[J].中华老年多器官疾病杂志,2023,22(4):284~289
利拉鲁肽对糖尿病肾病大鼠NOD样受体热蛋白结构域相关蛋白3表达的影响
Effects of liraglutide on NOD-like receptor pyrin domain containing 3 expression in rat model of diabetic nephropathy
投稿时间:2022-06-19  
DOI:10.11915/j.issn.1671-5403.2023.04.058
中文关键词:  糖尿病肾病  利拉鲁肽  NOD样受体热蛋白结构域相关蛋白3
英文关键词:diabetic nephropathy  liraglutide  NLRP3 This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region
基金项目:内蒙古自治区自然科学基金(2019MS08178);内蒙古医科大学科技百万工程联合项目[YKD2018KJBW(LH)077]
作者单位E-mail
马秀琦 内蒙古科技大学包头医学院,内蒙古自治区 包头 014040  
薛君 内蒙古包钢医院老年病科,内蒙古自治区 包头 014010 byxuejun@sina.com 
张莹 内蒙古科技大学包头医学院,内蒙古自治区 包头 014040  
武学慧 内蒙古科技大学包头医学院,内蒙古自治区 包头 014040  
张雅楠 内蒙古包钢医院老年病科,内蒙古自治区 包头 014010  
蔡志杰 内蒙古包钢医院老年病科,内蒙古自治区 包头 014010  
闫锐晶 内蒙古包钢医院老年病科,内蒙古自治区 包头 014010  
摘要点击次数: 148
全文下载次数: 104
中文摘要:
      目的 探讨利拉鲁肽是否通过抑制NOD样受体热蛋白结构域相关蛋白3(NLRP3)的活化在糖尿病肾病(DN)中发挥肾脏保护作用。方法 22只4周龄的Wistar品系雄性大鼠随机分为正常对照组(n=6)、利拉鲁肽组(n=8)和生理盐水组(n=8)。利拉鲁肽组予利拉鲁肽200μg/(kg·d)皮下注射,生理盐水组予等体积的生理盐水皮下注射,正常对照组不做任何处理,共治疗4周。治疗结束后检测大鼠体质量、24h尿总蛋白定量(UTP)、空腹血糖(FBG)、甘油三酯(TG)、胆固醇(TC)、血尿素氮(BUN)、血肌酐(SCr)等生化指标,各组大鼠肾组织进行苏木素-伊红染色(HE),光镜下观察肾组织病理形态学改变,Western blot检测肾组织中NLRP3炎症小体相关蛋白表达,酶联免疫吸附试验(ELISA)检测血清白细胞介素-18(IL-18)及血清白细胞介素-1β(IL-1β)的水平。采用SPSS 26.0统计软件和Graph Prism 9.0软件进行分析及绘图。计量资料多组间比较采用单因素方差分析,组内两两比较采用Tukey检验。结果 利拉鲁肽组大鼠FBG、UTP、BUN、SCr、TC、TG等生化指标水平较生理盐水组改善(P<0.01)。肾脏组织病理切片提示正常对照组肾小球、肾小管结构正常;生理盐水组可见肾小球体积增大、结构紊乱,系膜外基质增多,基底膜增厚明显;利拉鲁肽组大鼠肾脏病理变化减轻。Western blot检测提示经过利拉鲁肽的干预,NLRP3炎症小体相关蛋白的表达明显低于生理盐水组;ELISA检测提示生理盐水组IL-18、IL-1β水平明显增加,经利拉鲁肽干预后,IL-18、IL-1β水平下降。结论 利拉鲁肽可改变糖尿病肾病大鼠的疾病进程,这可能与利拉鲁肽抑制NLRP3炎症小体的激活有关。
英文摘要:
      Objective To investigate whether liraglutide plays a protective role in diabetic nephropathy (DN) by inhibiting the activation of NOD-like receptor pyrin domain containing 3 (NLRP3). Methods Twenty-two male Wistar rats (4 weeks old) were randomly divided into normal control group (n=6), liraglutide group (n=8) and normal saline group (n=8). After DN model was established, the rats of the liraglutide group were subcutaneously injected with 200 μg/(kg·d) liraglutide, those from the normal saline group were subcutaneously injected with same volume of normal saline, and those of the normal control group received no treatment. After 4 weeks′ treatment, body mass, 24 h urinary total protein (UTP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr) and other biochemical indexes were detected. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of renal tissue. The expression of NLRP3 inflammasome-related proteins in renal tissue was measured by Western blot, and the serum levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). SPSS statistics 26.0 and Graph Prism 9.0 software were used for analysis and mapping. One-way ANOVA was employed for intergroup comparison for measurement data, and Tukey test was adopted for intra-group comparison. Results Liraglutide intervention improved the levels of FBG, UTP, BUN, SCr, TC and TG when compared with those in normal saline group (P<0.01). Pathological observation displayed that normal structure of glomeruli and tubules were observed in the normal control group, increased glomerular volume and structure, extramembranous matrix, and significant thickening in basement membrane were seen in the normal saline group, and the pathological changes of the kidneys were alleviated in the liraglutide group. Western blot assay indicated that the protein expression levels of NLRP3 inflammasome-related proteins were significantly lower in the liraglutide group than the normal saline group. The results of ELISA showed that the levels of IL-18 and IL-1β were significantly increased in the normal saline group, but decreased after liraglutide intervention. Conclusion Liraglutide alters disease progression in DN rats, which may be related to its inhibition of NLRP3 inflammasome activation.
查看全文    下载PDF阅读器
关闭