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[人参皂苷Rg_1通过抑制2型糖尿病小鼠NLRP3炎性小体对糖尿病视网膜病变的保护作用]

[Protective effect of ginsenoside Rg_1 aganist diabetic retinopathy by inhibiting NLRP3 inflammasome in type 2 diabetic mice].

作者信息

Li Bin, Zhang Da-Chuan, Li Xue-Wang, Dong Xia-Nan, Li Wei-Ping, Li Wei-Zu

机构信息

Department of Ophthalmology, the Third People's Hospital of Hefei Hefei 230022, China.

Department of Pharmacology/Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education/Pharmacology 3rd Grade Laboratory of State Administration of Traditional Chinese Medicine, Anhui Medical University Hefei 230032, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2022 Jan;47(2):476-483. doi: 10.19540/j.cnki.cjcmm.20210926.401.

DOI:10.19540/j.cnki.cjcmm.20210926.401
PMID:35178992
Abstract

Ginsenoside Rg_1, one of the main active components of precious traditional Chinese medicine Ginseng Radix et Rhizoma, has the anti-oxidative stress, anti-inflammation, anti-aging, neuroprotection, and other pharmacological effects. Diabetic retinopathy(DR), the most common complication of diabetes, is also the main cause of impaired vision and blindness in the middle-aged and the elderly. The latest research shows that ginsenoside Rg_1 can protect patients against DR, but the protection and the mechanism are rarely studied. This study mainly explored the protective effect of ginsenoside Rg_1 against DR in type 2 diabetic mice and the mechanism. High fat diet(HFD) and streptozotocin(STZ) were used to induce type 2 diabetes in mice, and hematoxylin-eosin(HE) staining was employed to observe pathological changes in the retina of mice. The immunohistochemistry was applied to study the localization and expression of nucleotide-binding oligomerization domain-like receptors 3(NLRP3) and vascular endothelial growth factor(VEGF) in retina, and Western blot was used to detect the expression of nuclear factor-kappa B(NF-κB), p-NF-κB, NLRP3, caspase-1, interleukin-1β(IL-1β), transient receptor potential channel protein 6(TRPC6), nuclear factor of activated T-cell 2(NFAT2), and VEGF in retina. The results showed that ginsenoside Rg_1 significantly alleviated the pathological injury of retina in type 2 diabetic mice. Immunohistochemistry results demonstrated that ginsenoside Rg_1 significantly decreased the expression of NLRP3 and VEGF in retinal ganglion cells, middle plexiform layer, and outer plexiform layer in type 2 diabetic mice. According to the Western blot results, ginsenoside Rg_1 significantly lowered the expression of p-NF-κB, NLRP3, caspase-1, IL-1β, TRPC6, NFAT2, and VEGF in retina of type 2 diabetic mice. These findings suggest that ginsenoside Rg_1 can significantly alleviate DR in type 2 diabetic mice, which may be related to inhibition of NLRP3 inflammasome and VEGF. This study provides experimental evidence for the clinical application of ginsenoside Rg_1 in the treatment of DR.

摘要

人参皂苷Rg_1是名贵中药材人参的主要活性成分之一,具有抗氧化应激、抗炎、抗衰老、神经保护等药理作用。糖尿病视网膜病变(DR)是糖尿病最常见的并发症,也是中老年人群视力受损和失明的主要原因。最新研究表明,人参皂苷Rg_1可保护患者预防DR,但对其保护作用及机制的研究较少。本研究主要探讨人参皂苷Rg_1对2型糖尿病小鼠DR的保护作用及其机制。采用高脂饮食(HFD)和链脲佐菌素(STZ)诱导小鼠患2型糖尿病,并用苏木精-伊红(HE)染色观察小鼠视网膜的病理变化。应用免疫组织化学研究核苷酸结合寡聚化结构域样受体3(NLRP3)和血管内皮生长因子(VEGF)在视网膜中的定位和表达,并用蛋白质免疫印迹法检测视网膜中核因子-κB(NF-κB)、磷酸化核因子-κB(p-NF-κB)、NLRP3、半胱天冬酶-1(caspase-1)、白细胞介素-1β(IL-1β)、瞬时受体电位通道蛋白6(TRPC6)、活化T细胞核因子2(NFAT2)和VEGF的表达。结果表明,人参皂苷Rg_1可显著减轻2型糖尿病小鼠视网膜的病理损伤。免疫组织化学结果显示,人参皂苷Rg_1可显著降低2型糖尿病小鼠视网膜神经节细胞、中间丛状层和外丛状层中NLRP3和VEGF的表达。根据蛋白质免疫印迹结果,人参皂苷Rg_1可显著降低2型糖尿病小鼠视网膜中p-NF-κB、NLRP3、caspase-1、IL-1β、TRPC6、NFAT2和VEGF的表达。这些研究结果表明,人参皂苷Rg_1可显著减轻2型糖尿病小鼠的DR,这可能与抑制NLRP3炎性小体和VEGF有关。本研究为人参皂苷Rg_1治疗DR的临床应用提供了实验依据。

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引用本文的文献

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Clinical observations and mechanistic insights of traditional Chinese medicine in the management of diabetic retinopathy.糖尿病视网膜病变的中医药管理的临床观察和机制见解。
Pharm Biol. 2024 Dec;62(1):529-543. doi: 10.1080/13880209.2024.2369292. Epub 2024 Jun 26.
2
Role of the inflammasome in insulin resistance and type 2 diabetes mellitus.炎症小体在胰岛素抵抗和 2 型糖尿病中的作用。
Front Immunol. 2023 Mar 13;14:1052756. doi: 10.3389/fimmu.2023.1052756. eCollection 2023.