Mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy by regulating interleukin-33/suppression of tumorigenicity 2 signaling pathway
-
摘要:目的
探讨circ-001209调控白细胞介素-33/生长刺激表达基因2蛋白(IL-33/ST2)信号通路对糖尿病视网膜病变(DR)大鼠视网膜微血管生成的作用机制。
方法将50只大鼠随机分为Col组、DR组、si-circ-NC组、si-circ-001209组和si-circ-001209+IL-33组, 每组10只。检测大鼠空腹血糖(FPG)和血清空腹胰岛素(FINS)水平; 采用荧光素眼底血管造影术(FFA)检测视网膜血管生成; 采用酶联免疫吸附试验(ELISA)检测血清中血管生成相关因子及炎症因子水平; 采用苏木精-伊红(HE)染色检测视网膜组织病理学变化; 采用过碘酸-Schiff反应(PAS)染色检测视网膜微血管生成数; 采用蛋白质印迹法检测视网膜组织中IL-33、ST2、血管内皮生长因子(VEGF)、低氧诱导因子-1α(HIF-1α)、细胞间黏附分子-1(ICAM-1)蛋白表达。
结果与Col组比较, DR组、si-circ-NC组FPG, FINS, 血清VEGF、血管生成素-1(Ang-1)、IL-6、IL-33、肿瘤坏死因子-α(TNF-α)水平，微血管生成数以及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达均升高，差异有统计学意义(P < 0.05); si-circ-001209组FPG, FINS, 血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平，微血管生成数以及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达均低于si-circ-NC组，差异有统计学意义(P < 0.05); si-circ-001209+IL-33组FPG, FINS, 血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平，微血管生成数及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达高于si-circ-001209组，差异有统计学意义(P < 0.05)。
结论敲减circ-001209可抑制DR大鼠视网膜微血管生成，作用机制可能与抑制IL-33/ST2信号通路激活、降低炎症水平有关。
Abstract:ObjectiveTo investigate the mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy (DR) by regulating the interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) signaling pathway.
MethodsFifty rats were randomly divided into Col group, DR group, si-circ-NC group, si-circ-001209 group, and si-circ-001209+IL-33 group, with 10 rats in each group. The levels of fasting plasma glucose (FPG) and fasting insulin (FINS) in rats were detected; fundus fluorescein angiography (FFA) was used to detect retinal angiogenesis; the enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of angiogenesis-related factors and inflammatory factors in serum; the hematoxylin-eosin (HE) staining was used to detect histopathological changes in the retina; the periodic acid-Schiff (PAS) staining was used to detect the number of retinal microvascular formations; the Western blotting was used to detect the protein expression levels of IL-33, ST2, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and intercellular adhesion molecule-1 (ICAM-1) in retinal tissues.
ResultsCompared with the Col group, the DR group and si-circ-NC group showed significant increase in levels of FPG, FINS, serum VEGF, angiopoietin-1 (Ang-1), IL-6, IL-33, tumor necrosis factor-α (TNF-α), the number of microvascular formation, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues (P < 0.05); the si-circ-001209 group showed significant decrease in levels of FPG, FINS, serum VEGF, Ang-1, IL-6, IL-33, TNF-α, the number of microvascular formation, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues compared with the si-circ-NC group (P < 0.05); the si-circ-001209+IL-33 group showed significant increase in levels of FPG, FINS, serum VEGF, Ang-1, IL-6, IL-33, TNF-α, the number of microvascular formations, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues compared with the si-circ-001209 group (P < 0.05).
ConclusionsKnockdown of circ-001209 can inhibit retinal angiogenesis in rats with DR, potentially through inhibiting the activation of the IL-33/ST2 signaling pathway and reducing inflammation.
-
-
![]()
图 1 各组大鼠FPG和FINS比较(n=10)
A: 各组大鼠血清FPG比较; B: 各组大鼠FINS比较。
与Col组比较, *P < 0.05; 与si-circ-NC组比较, #P < 0.05; 与si-circ-001209组比较, △P < 0.05。![]()
图 3 各组大鼠血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平比较(n=10)
A: 血清VEGF水平比较; B: 血清Ang-1水平比较; C: 血清IL-6水平比较; D: 血清IL-33水平比较; E: 血清TNF-α水平比较。
与Col组比较, *P < 0.05; 与si-circ-NC组比较, #P < 0.05; 与si-circ-001209组比较, △P < 0.05。 -
[1] CHEN Y, SCHLOTTERER A, KUROWSKI L, et al. miRNA-124 prevents rat diabetic retinopathy by inhibiting the microglial inflammatory response[J]. Int J Mol Sci, 2023, 24(3): 2291. doi: 10.3390/ijms24032291
[2] MILLS S A, JOBLING A I, DIXON M A, et al. Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy[J]. Proc Natl Acad Sci U S A, 2021, 118(51): e2112561118. doi: 10.1073/pnas.2112561118
[3] CHEN Y Q, YAO G H, TONG J, et al. MSC-derived small extracellular vesicles alleviate diabetic retinopathy by delivering miR-22-3p to inhibit NLRP3 inflammasome activation[J]. Stem Cells, 2024, 42(1): 64-75. doi: 10.1093/stmcls/sxad078
[4] LI Y, ZHU L P, CAI M X, et al. TGR5 supresses cGAS/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy[J]. Cell Death Dis, 2023, 14(9): 583. doi: 10.1038/s41419-023-06111-5
[5] ZHOU Y L, XU Z D, LIU Z Q. Role of IL-33-ST2 pathway in regulating inflammation: current evidence and future perspectives[J]. J Transl Med, 2023, 21(1): 902. doi: 10.1186/s12967-023-04782-4
[6] MEHRABI NASAB E, HASSANZADEH MAKOEI R, AGHAJANI H, et al. IL-33/ST2 pathway as upper-hand of inflammation in allergic asthma contributes as predictive biomarker in heart failure[J]. ESC Heart Fail, 2022, 9(6): 3785-3790. doi: 10.1002/ehf2.14111
[7] GUNGOR O, UNAL H U, GUCLU A, et al. IL-33 and ST2 levels in chronic kidney disease: associations with inflammation, vascular abnormalities, cardiovascular events, and survival[J]. PLoS One, 2017, 12(6): e0178939. doi: 10.1371/journal.pone.0178939
[8] YANG J H, TAN C Y, WANG Y, et al. The circRNA MKLN1 regulates autophagy in the development of diabetic retinopathy[J]. Biochim Biophys Acta Mol Basis Dis, 2023, 1869(8): 166839. doi: 10.1016/j.bbadis.2023.166839
[9] ZHANG Y T, HU J P, QU X Y, et al. Circular RNA RSU1 promotes retinal vascular dysfunction by regulating miR-345-3p/TAZ[J]. Commun Biol, 2023, 6(1): 719. doi: 10.1038/s42003-023-05064-x
[10] WANG F, ZHANG M X. Circ_001209 aggravates diabetic retinal vascular dysfunction through regulating miR-15b-5p/COL12A1[J]. J Transl Med, 2021, 19(1): 294. doi: 10.1186/s12967-021-02949-5
[11] LI H D, LIU C Y, ZHANG J Y, et al. The association of homocysteine level with the risk of diabetic nephropathy and diabetic retinopathy in NHANES[J]. Acta Diabetol, 2023, 60(7): 907-916. doi: 10.1007/s00592-023-02075-2
[12] JI F, ZHANG H J, GE Q. Effect of IP-10/CXCR3 signaling pathway on rats with diabetic retinopathy[J]. Cell Mol Biol, 2023, 69(11): 233-238. doi: 10.14715/cmb/2023.69.11.35
[13] WANG Y, ZHANG Y X, QU Y H, et al. eIF4A3-mediated circEHMT1 regulation in retinal microvascular endothelial dysfunction in diabetic retinopathy[J]. Microvasc Res, 2024, 151: 104612. doi: 10.1016/j.mvr.2023.104612
[14] WANG T, LI C P, SHI M, et al. Circular RNA circZNF532 facilitates angiogenesis and inflammation in diabetic retinopathy via regulating miR-1243/CARM1 axis[J]. Diabetol Metab Syndr, 2022, 14(1): 14. doi: 10.1186/s13098-022-00787-z
[15] AI X P, YU P L, LUO L L, et al. Berberis dictyophylla F. inhibits angiogenesis and apoptosis of diabetic retinopathy via suppressing HIF-1α/VEGF/DLL-4/Notch-1 pathway[J]. J Ethnopharmacol, 2022, 296: 115453. doi: 10.1016/j.jep.2022.115453
[16] CHEN X, WANG Y, WANG J N, et al. Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy[J]. EMBO Mol Med, 2024, 16(2): 294-318. doi: 10.1038/s44321-024-00025-1
[17] 苏杰, 杨馥宇, 李猛, 等. 京尼平苷对糖尿病视网膜病变大鼠视网膜微血管生成的影响及其机制[J]. 眼科新进展, 2023, 43(9): 703-707, 711. [18] TANG L, XU G T, ZHANG J F. Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy[J]. Neural Regen Res, 2023, 18(5): 976-982. doi: 10.4103/1673-5374.355743
[19] 韩璐, 黄铁军, 马雅琪, 等. 白介素33及其受体ST2与心脏重塑关系的研究进展[J]. 湖北科技学院学报: 医学版, 2022, 36(5): 448-451. [20] 帅天姣, 王彤彤, 谢伟, 等. 黄芩苷调节IL-33/ST2信号通路对糖尿病视网膜病变大鼠视网膜新生血管生成的影响[J]. 眼科新进展, 2022, 42(9): 685-689. -
期刊类型引用(27)
1. 朱瑞敬. 老年下肢骨折手术患者应用腰硬联合麻醉对认知功能、疼痛程度的影响. 中国现代药物应用. 2025(04): 28-32 . 
百度学术
2. 王超平，吕秉乐，包伟东，孙永强，陈森. 不同麻醉方法对高龄膝关节单髁置换患者术后早期认知及应激反应的影响. 临床医学研究与实践. 2024(14): 25-28 . 百度学术
3. 张衍平，李现虎，李康. 超声引导下神经阻滞联合全麻用于老年下肢骨折术中的效果. 医学临床研究. 2024(04): 569-571+575 . 百度学术
4. 孙忠锋，王昭君，田保贵. 股神经联合股外侧皮神经阻滞麻醉与腰硬联合麻醉在老年危重症患者下肢骨折手术中的效果. 中国老年学杂志. 2023(02): 313-317 . 百度学术
5. 江翠红. 不同椎管内麻醉方法对老年下肢骨折患者循环功能的影响对比. 基层医学论坛. 2023(11): 145-148 . 百度学术
6. 杨昌雄，张合茂，王超，苟涛，刘光钊. 腰麻-硬膜外联合麻醉对老年下肢骨折患者术后镇痛及凝血功能的影响. 中国老年学杂志. 2023(14): 3401-3404 . 百度学术
7. 朱小宁，李雪，于芝. 腰硬联合麻醉对骨科手术患者血流动力学、疼痛程度和认知功能的影响. 中外医学研究. 2023(25): 67-70 . 百度学术
8. 顾礼萍. 腰硬联合麻醉对老年下肢手术患者MoCA评分及血流动力学的影响. 系统医学. 2023(20): 55-58 . 百度学术
9. 石丹，廖建辉，肖赵山. 腰硬联合麻醉在高龄股骨颈骨折术中的价值研究. 深圳中西医结合杂志. 2022(07): 65-67 . 百度学术
10. 李歌娟，周伟，梁艳宁. 多模式镇痛在老年骨科手术的应用效果及对患者认知功能的影响. 医药论坛杂志. 2022(19): 53-55+59 . 百度学术
11. 陈平，刘迎春，朱燕，朱菁. 腰硬联合麻醉在老年骨折患者中的应用. 中外医疗. 2022(30): 56-59 . 百度学术
12. 陈丽花，赵彦春. 超声引导下股神经-股外侧皮神经阻滞治疗髌骨骨折患者临床观察. 社区医学杂志. 2021(04): 231-234 . 百度学术
13. 赵翠英，王全涌，赵鑫. 腰硬联合麻醉对股骨颈骨折手术患者平均动脉压、认知功能及舒适度的影响. 河南外科学杂志. 2021(02): 139-140 . 百度学术
14. 付林芳，王建平，钟乘坊，何素萍. 右美托咪定在腰硬联合麻醉中对老年骨科手术麻醉效果及血压的影响观察. 基层医学论坛. 2021(17): 2381-2383 . 百度学术
15. 徐秀华. 全身麻醉和腰硬联合麻醉对老年下肢骨折手术患者认知功能的影响. 智慧健康. 2021(25): 54-56 . 百度学术
16. 李春伟. 全凭静脉麻醉与腰-硬联合麻醉用于老年髋关节置换术患者的临床对比研究. 河南外科学杂志. 2021(06): 89-91 . 百度学术
17. 王波. 腰-硬联合麻醉与全身麻醉在老年下肢骨折手术患者中的疗效对比. 中国医药指南. 2021(36): 53-55 . 百度学术
18. 张瑞圃. 腰硬联合麻醉对老年骨科手术患者血流动力学及短期认知功能的影响. 黑龙江医学. 2020(04): 503-505 . 百度学术
19. 杜刚. 腰硬联合麻醉在老年下肢骨折患者手术中的应用效果分析. 临床医药文献电子杂志. 2020(40): 25 . 百度学术
20. 陈上平. 老年下肢骨折应用腰硬联合麻醉与全身麻醉的效果对比. 基层医学论坛. 2020(17): 2446-2447 . 百度学术
21. 郭敏. 腰硬联合麻醉对老年膝骨性关节炎患者术后认知功能的影响. 临床医学工程. 2020(08): 1059-1060 . 百度学术
22. 李小明，王巧丽. 腰麻-硬膜外联合阻滞在高龄患者股骨粗隆间骨折术中的应用效果及对术后认知功能的影响. 河南医学研究. 2020(20): 3709-3711 . 百度学术
23. 姜皓. 探析在老年患者下肢手术中实施腰-硬联合麻醉的效果. 系统医学. 2020(11): 46-48 . 百度学术
24. 樊航行，张大志，段崇珍. 老年下肢骨折手术患者的麻醉方式选择. 实用临床医药杂志. 2020(16): 82-84 . 本站查看
25. 张智卿，彭春潮，王鑫，才仁卓玛，张雯. 高海拔地区≥70岁老年人术中腰硬联合麻醉的应用效果及安全性分析. 现代生物医学进展. 2020(17): 3345-3348 . 百度学术
26. 金晓伟，陈千煌，蒋毅，许兵. 胫骨骨折术中超声引导区域神经阻滞麻醉、腰硬联合麻醉的临床效果. 浙江创伤外科. 2020(03): 416-417 . 百度学术
27. 龚小刚. 腰硬联合麻醉在单侧下肢骨关节手术患者中的应用. 医疗装备. 2020(19): 71-72 . 百度学术
其他类型引用(1)
下载:
计量
- 文章访问数: 29
- HTML全文浏览量: 4
- PDF下载量: 4
- 被引次数: 28
苏公网安备 32100302010246号