| 康文媛,杨洋,张然,等.微囊蛋白 -1调节铁死亡介导的线粒体稳态改善 2型糖尿病伴高血压的肾功能损伤[J].安徽医药,2024,28(9):1767-1772. |
| 微囊蛋白 -1调节铁死亡介导的线粒体稳态改善 2型糖尿病伴高血压的肾功能损伤 |
| Caveolin-1 ameliorates renal impairment in type 2 diabetes with hypertension regulating iron death-mediated mitochondrial homeostasis |
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| DOI：10.3969/j.issn.1009-6469.2024.09.016 |
| 中文关键词: 糖尿病， 2型 高血压 微囊蛋白 -1 铁死亡 线粒体功能 肾功能 |
| 英文关键词: Diabetes mellitus,type 2 Hypertension Caveolin-1 Iron death Mitochondrial function Re-nal function |
| 基金项目:石家庄市科技计划项目( 221460393) |
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| 中文摘要: |
| 目的探究微囊蛋白 -1(caveolin-1，Cav-1)通过调节铁死亡介导的线粒体稳态来对 2型糖尿病( T2DM)伴发高血压大鼠肾功能损伤的改善作用。方法于 2021年 5月至 2022年 5月采用自发性高血压大鼠( SHR)建立 T2DM大鼠模型，将大鼠按随机数字表法分为对照组、 SHR+T2DM组、 pCDNA3.1(+)-NC组和 pCDNA3.1(+)-Cav-1组，每组 10只。测定大鼠收缩压、空腹血糖值( FBG)、空腹胰岛素( FINS)、糖化血红蛋白( GHbA1C)浓度、评价胰岛素抵抗指数( HOMA-IR)、血肌酐、尿素氮含量，并计算尿清蛋白与肌酐比值( UACR)HE染色检测肾组织病理学变化；检测肾组织中亚铁离子( Fe2+)、丙二醛含量及超氧化物歧化酶( SOD)活性；二氢乙锭( DHE)荧光染色法检测肾组织中活性氧水平；线粒体膜电位荧光探针( JC-1法)检测肾组织中线粒体膜电位( MMP)水平；蛋白质印迹法检测肾组织中谷胱甘肽过氧化酶 4(GPX4)、 x-CT蛋白表达。结果 SHR+T2DM组收缩压(189.46±7.51)mmHg、FBG(23.46±1.28)mmol/L、FINS(1.62±0.15)mU/L、HOME-IR(1.52±0.13)、 GHbA1C(689.31±45.81)nmol/L、血肌酐( 83.69±4.25)mmol/L、尿素氮( 19.32±2.54)mmol/L、UACR(76.51±8.09)、 Fe2+(0.45±0.05)mg/g、丙二醛( 58.32±3.26)nmol/ L、活性氧含量 23.46±1.84均高于对照组［( 110.34±5.26)mmHg、(5.12±0.94)mmol/L、(0.68±0.07)mU/L、0.31±0.04、(310.48±23.26)nmol/L、(32.08±3.61)mmol/L、(6.89±1.86)mmol/L、8.31±0.94、(0.13±0.02)mg/g、(15.68±2.15)nmol/L、1.31±0.23］，SOD活性( 11.56±1.62)U/mg、MMP水平 0.25±0.03、GPX4(0.35±0.04)和 x-CT蛋白 0.51±0.06表达均低于对照组［( 35.61±2.17)U/mg、0.62±0.08、1.00±0.10、1.00±0.09］(P<0.05)；和 SHR+T2DM组相比， pCDNA3.1(+)-Cav-1组收缩压( 136.27±6.09)mmHg、FBG(10.37±1.05)mmol/L、FINS(0.91±0.10)mU/L、HOME-IR(0.64±0.08)、 GHbA1C(426.17±25.94)nmol/L、血肌酐( 51.36±3.87) mmol/L、尿素氮( 10.71±2.18)mmol/L、UACR(38.62±4.18)、 Fe2+(0.18±0.03)mg/g、丙二醛( 21.39±2.64)nmol/L、活性氧含量 5.47±1.06均明显降低， SOD活性( 29.83±1.94)U/mg、MMP水平 0.51±0.06、GPX4(0.86±0.09)和 x-CT蛋白 0.91±0.08表达升高( P<0.05)。结论 Cav-1可通过抑制铁死亡来维持线粒体功能的稳态，进而对 T2DM合并 SHR大鼠的肾组织发挥保护作用。 |
| 英文摘要: |
| Objective To investigate the ameliorative effect of Caveolin-1 (Cav-1) on renal impairment in type 2 diabetes mellitus (T2DM) with hypertension by regulating iron death-mediated mitochondrial homeostasis.Methods A T2DM rat model was established from May 2021 to May 2022 using spontaneously hypertensive rats (SHR), and the rats were randomly numbered and tabulated into thecontrol group, SHR+T2DM group, pCDNA3.1(+)-NC group, and pCDNA3.1(+)-Cav-1 group, with 10 rats in each group. Systolic bloodpressure (SBP), fasting blood glucose value (FBG), fasting insulin (FINS), glycated hemoglobin (GHbA1C) concentration, homeostasismodel assessment of insulin resistance (HOMA-IR), blood creatinine (Cr), and blood urea nitrogen (BUN) levels were measured in therats, and the urinary ascorbic protein/creatinine ratio (UACR) was calculated. HE staining was used to detect the renal histopathologi-cal changes. Kidney tissue was tested for Fe2+, MDA content and SOD activity. Dihydroethidium (DHE) fluorescence staining was usedto detect reactive oxygen species (ROS) level in renal tissue, JC-1 method to detect mitochondrial membrane potential (MMP) level inrenal tissue, and protein blotting to detect glutathione peroxidase 4 (GPX4) and x-CT protein expressions in renal tissue.Results SBP, FBG,FINS, HOME-IR, GHbA1C, Cr, BUN, UACR, Fe2+, MDA, and ROS levels in the SHR+T2DM group were higher than those in the control group [(189.46±7.51) mmHg vs. (110.34±5.26) mmHg, (23.46±1.28) mmol/L vs. (5.12±0.94) mmol/L, (1.62±0.15) mU/L vs.(0.68±0.07) mU/L, 1.52±0.13 vs. 0.31±0.04, (689.31±45.81) nmol/L vs. (310.48±23.26) nmol/L, (83.69±4.25) mmol/L vs. (32.08±3.61) mmol/L, (19.32±2.54) mmol/L vs. (6.89±1.86) mmol/L, 76.51±8.09 vs. 8.31±0.94, (0.45±0.05) mg/g vs. (0.13±0.02)mg/g, (58.32±3.26) nmol/L vs. (15.68±2.15) nmol/L, 23.46±1.84 vs. 1.31±0.23], while SOD activity, MMP levels, GPX 4 and x-CT protein in the SHR+ T2DM group were lower than those in the control group [(11.56±1.62) U/mg vs. (35.61±2.17) U/mg, 0.25±0.03 vs. 0.62±0.08, 0.35±0.04 vs. 1.00±0.10, 0.51±0.06 vs. 1.00±0.09] (P<0.05). Compared with the SHR+T2DM group, SBP, FBG, FINS, HOME-IR, GHbA1C, Cr, BUN, UACR, Fe2+ , MDA, and ROS levels in the pCDNA3.1(+ ) -Cav-1 group were significantly decreased [(136.27±6.09) mmHg,(10.37±1.05) mmol/L, (0.91±0.10) mU/L, 0.64±0.08, (426.17±25.94) nmol/L, (51.36±3.87) mmol/L, (10.71±2.18) mmol/L, 38.62±4.18,(0.18±0.03) mg/g, (21.39±2.64) nmol/L, and 5.47±1.06, respectively], while SOD activity, MMP level, GPX 4, and x-CT protein expres- sions were increased [(29.83±1.94) U/mg, 0.51±0.06, 0.86±0.09, and (0.91±0.08), respectively] (P<0.05).Conclusion Caveolin-1 can maintain the homeostasis of mitochondrial function by inhibiting iron death, which in turn exerts a protective effect on renal tissue inT2DM combined with SHR rats. |
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