基础医学与临床 ›› 2021, Vol. 41 ›› Issue (4): 484-489.

• 研究论文 • 上一篇    下一篇

膜联蛋白A1减轻1型糖尿病小鼠微血管并发症

边芳1, 李宁2, 李奇2, 李康3, 金雯4*   

  1. 1.陕西省友谊医院 内分泌科, 陕西 西安 710068;
    2.神经外科, 西安交通大学第一附属医院 陕西 西安 710061;
    3.肿瘤外科, 西安交通大学第一附属医院 陕西 西安 710061;
    4.陕西省人民医院 妇科, 陕西 西安 710068
  • 收稿日期:2020-04-17 修回日期:2020-10-19 出版日期:2021-04-05 发布日期:2021-04-05
  • 通讯作者: *18602930114@163.com
  • 基金资助:
    国家自然科学基金(81370069);陕西省重点研发计划(2019SF-152)

Annexin A1 alleviates microvascular complications in type 1 diabetic mice

BIAN Fang1, LI Ning2, LI Qi2, LI Kang3, JIN Wen4*   

  1. 1. Department of Endocrinology, Shaanxi Friendship Hospital, Xi'an 710068;
    2. Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061;
    3. Department of Surgical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061;
    4. Department of Gynaecology, Shaanxi Provincial People's Hospital, Xi'an 710068, China
  • Received:2020-04-17 Revised:2020-10-19 Online:2021-04-05 Published:2021-04-05
  • Contact: *18602930114@163.com

摘要: 目的 探讨膜联蛋白A1(ANXA1)在预防及减轻1型糖尿病(T1D)微血管并发症方面的潜在价值。方法 检测T1D患者和健康体检者血浆中ANXA1的水平;用人重组ANXA1(hrANXA1)治疗T1D小鼠8周;给药完成后对小鼠进行口服葡萄糖耐量试验(OGTT)。超声心动图评估小鼠的左室射血分数(EF)和左室短轴缩短率(FS);Au400检测各组小鼠血清尿素和肌酐水平;ELISA检测胰岛素、尿白蛋白和ANXA1水平;对小鼠心脏和肾脏组织进行PAS染色或天狼星红染色;Western blot检测蛋白激酶B(Akt)/p-Akt、p38/p-p38、c-Jun氨基末端激酶(JNK)/p-JNK、细胞外信号调节激酶(ERK1/2)/p-ERK1/2的表达。结果 与健康体检者相比,T1D患者血浆ANXA1的水平降低,而C反应蛋白(CRP)水平升高(P<0.05)。hrANXA1降低了T1D小鼠葡萄糖耐量试验(OGTT)曲线下面积(AUC)并提高了血清胰岛素水平(P<0.05)。hrANXA1提高了小鼠的左室射血分数(EF)和左室短轴缩短率(FS)(P<0.05);hrANXA1降低了小鼠的血清尿白蛋白与肌酐比值(ACR)和尿素水平(P<0.05)。hrANXA1促进了小鼠心脏和肾脏组织中Akt的磷酸化,并抑制了p38、JNK和ERK1/2的磷酸化(P<0.05)。结论 ANXA1对T1D小鼠的心脏和肾脏的保护作用与抑制MAPK信号通路和激活Akt生存途径有关。

关键词: 1型糖尿病, 膜联蛋白A1, 微血管并发症, MAPK信号通路, Akt生存途径

Abstract: Objective To investigate the potential value of annexin A1 (ANXA1) in preventing and alleviating microvascular complications in type 1 diabetes (T1D). Methods Plasma ANXA1 level was detected in T1D patients and healthy people. T1D mice were treated with human recombinant ANXA1 (rANXA1) for 8 weeks. After the administration, the mice were subjected to the oral glucose tolerance test (OGTT). The left ventricular ejection fraction (EF) and left ventricular fraction shortening (FS) of the mice were evaluated by echocardiography. Serum urea and creatinine of mice in each group were detected by Au400. The concentration of insulin, urinary albumin and ANXA1 were measured by ELISA. The heart and kidney tissues of mice were stained with PAS or Sirius red. Western blot was used to detect protein kinase B (Akt)/p-Akt, p38/p-p38, c-Jun amino terminal kinase (JNK)/p-JNK, and extracellular signal-regulated kinase (ERK1/2)/p-ERK1/2 expression level. Results Comparing with healthy people, the plasma ANXA1 level of T1D patients decreased, while the level of C-reactive protein (CRP) increased (P<0.05). hrANXA1 reduced the area under the curve (AUC) of the T1D mouse glucose tolerance test (OGTT) and increased serum insulin level(P<0.05). hrANXA1 increased the left ventricular ejection fraction (EF) and left ventricular short axis shortening rate (FS) of mice (P<0.05); hrANXA1 reduced the serum urinary albumin to creatinine ratio (ACR) and urea level of mice (P<0.05). hrANXA1 promoted the phosphorylation of Akt in mouse heart and kidney tissues, and inhibited the phosphorylation of p38, JNK and ERK1/2 (P<0.05). Conclusions The protective effect of ANXA1 on the heart and kidney of T1D mice is attributed to the inhibition of MAPK signaling pathway and activation of Akt survival pathway.

Key words: type 1 diabetes, annexin A1, microvascular complications, MAPK signaling pathway, Akt survival pathway

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