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| Effect of ginkgo diterpenoid lactone on retinopathy in diabetic rats based on TLR4/NF-κB signal pathway |
| Hits 458 Download times 5189 Received:January 18, 2023 |
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| DOI
10.11656/j.issn.1672-1519.2023.05.20 |
| Key Words
ginkgo diterpene lactone;diabetic mellitus;retina;TLR4/NF-κB signal pathway;inflammation;apoptosis |
| Author Name | Affiliation | | GAO Ming | Fourth People's Hospital of Langfang, Langfang 065700, China | | XU Lili | Fourth People's Hospital of Langfang, Langfang 065700, China | | WANG Licun | Fourth People's Hospital of Langfang, Langfang 065700, China | | DING Cheng | Fourth People's Hospital of Langfang, Langfang 065700, China | | ZHAO Jing | Fourth People's Hospital of Langfang, Langfang 065700, China | | DENG Kun | Fourth People's Hospital of Langfang, Langfang 065700, China | | YANG Lijun | Fourth People's Hospital of Langfang, Langfang 065700, China |
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| Abstract
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| [Objective] To investigate the effect of ginkgo diterpene lactone (GDL) on retinopathy in diabetic mellitus rats, and explore its mechanism based on toll like receptor 4/nuclear factor-κB (TLR4/NF-κB) signal pathway.[Methods] The diabetic mellitus retinopathy rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin after high sugar and high fat diet, and set model group, GDL (2.3 mg/kg) group, TAK242 (TLR4 inhibitor, 3 mg/kg) group and GDL+TAK242 (2.3 mg/kg+3 mg/kg) group; and another normal group was setup. After 14 days of intraperitoneal injection of the drugs once a day in each group, the fasting blood glucose (FBG), retinal thickness, retinal vascular permeability were measured; the pathological changes and cell apoptosis of retina were observed by HE staining and TUNEL staining; the content of inflammatory factor [interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor α (TNF-α)] in retinal were detected by ELISA method; the expression of TLR4, NF-κB, p-NF-κB, NF-κB Inhibitor (IκBα), p-IκBα, high mobility group protein B1(HMGB1), B-lymphomatoma-2 gene(Bcl-2), Bcl-2 related X protein(Bax) were detected by Western blot.[Results] Compared with the model group, the FBG level, and vascular permeability were decreased in GDL group, TAK242 group and GDL+TAK242 group, the retinal thickness was increased(P < 0.05);the pathological changes such as cells number decreased, arrangement disordered, unclear stratification, edema and inflammatory infiltration of retinal retinal ganglion cell layer and inner nuclear layer were significantly reduced, and retinal cells apoptosis was significantly improved; the content of IL-1β, IL-6, IL-8, TNF-α in retinal were decreased(P < 0.05);the expression of TLR4, p-NF-κB, p-IκBα, HMGB1, Bax and the ratio of p-NF-κB/NF-κB, p-IκBα/IκBα, Bax/Bcl-2 were decreased(P < 0.05);the expression of Bcl-2 was increased(P < 0.05). The regulating effect of GDL+TAK242 group on the indexes above of diabetic mellitus rats was significantly better than that of GDL group and TAK242 group(P < 0.05).[Conclusion] GDL can inhibit the inflammatory reaction and cell apoptosis, reduce the retinal vascular permeability and alleviate the pathological changes of the retina in diabetic mellitus rats, which mechanism may be related to the inhibition of TLR4/NF-κB signal pathway activation. |
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