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印楝素通过抑制TLR4/NF-κB信号通路改善链脲佐菌素诱导的大鼠糖尿病视网膜病变。

Nimbolide ameliorates the streptozotocin-induced diabetic retinopathy in rats through the inhibition of TLR4/NF-κB signaling pathway.

作者信息

Shu Xiangwen, Hu Yali, Huang Chao, Wei Ning

机构信息

Second Department of Ophthalmology, Second People's Hospital of Jinan, Jinan 250001, China.

Department of Ophthalmology, Binzhou Hospital of Traditional Chinese Medicine, Binzhou 256600, China.

出版信息

Saudi J Biol Sci. 2021 Aug;28(8):4255-4262. doi: 10.1016/j.sjbs.2021.06.039. Epub 2021 Jun 19.

DOI:10.1016/j.sjbs.2021.06.039
PMID:34354407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8324995/
Abstract

BACKGROUND

Diabetic retinopathy (DR) is a common problem in the diabetic patients due to the high blood glucose level. DR affects more number of diabetic patients worldwide with irreversible vision loss.

OBJECTIVE

The current investigation was focused to reveal the therapeutic actions of nimbolide against the streptozotocin (STZ)-provoked DR in rats through inhibition of TLR4/NF-κB pathway.

METHODOLOGY

DR was provoked to the rats through administering a single dose of STZ (60 mg/kg) intraperitoneally. The DR rats were then supplemented with the 50 mg/kg of nimbolide for 60 days. The bodyweight and blood glucose level was measured using standard methods. The lipid profiles (cholesterol, TG, LDL, and HDL), inflammatory markers, and antioxidants level was detected using respective kits. The level of MCP-1, VEGF, and MMP-9 was quantified using kits. The morphometric analysis of retinal tissues were done. The mRNA expressions of target genes were studied using RT-PCR assay.

RESULTS

Nimbolide treatment effective decreased the food intake and blood glucose, and improved the bodyweight of STZ-provoked animals. The levels of pro-inflammatory mediators, cholesterol, TG, LDL, and HDL, MCP-1, VEGF, and MMP-9 was remarkably suppressed by the nimbolide treatment. Nimbolide also improved the antioxidants, retinal thickness and cell numbers. The TLR4/NF-κB pathway was appreciably inhibited by the nimbolide.

CONCLUSION

Overall, our findings demonstrated that the nimbolide attenuated the STZ-provoked DR in rats through inhibiting the TLR4/NF-κB pathway.

摘要

背景

由于高血糖水平,糖尿病视网膜病变(DR)是糖尿病患者中的常见问题。DR在全球影响着更多的糖尿病患者,并导致不可逆的视力丧失。

目的

本研究旨在通过抑制TLR4/NF-κB途径,揭示印楝素对链脲佐菌素(STZ)诱导的大鼠DR的治疗作用。

方法

通过腹腔注射单剂量STZ(60mg/kg)诱导大鼠发生DR。然后给DR大鼠补充50mg/kg印楝素,持续60天。使用标准方法测量体重和血糖水平。使用相应试剂盒检测血脂谱(胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白)、炎症标志物和抗氧化剂水平。使用试剂盒定量检测MCP-1、VEGF和MMP-9的水平。对视网膜组织进行形态计量分析。使用RT-PCR检测法研究靶基因的mRNA表达。

结果

印楝素治疗有效降低了STZ诱导动物的食物摄入量和血糖,并改善了体重。印楝素治疗显著抑制了促炎介质、胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白、MCP-1、VEGF和MMP-9的水平。印楝素还改善了抗氧化剂水平、视网膜厚度和细胞数量。印楝素明显抑制了TLR4/NF-κB途径。

结论

总体而言,我们的研究结果表明,印楝素通过抑制TLR4/NF-κB途径减轻了STZ诱导的大鼠DR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/3878509eb009/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/27e54d25fbf4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/384902878115/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/021158b0b069/gr3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/2e78cf86d105/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/c607d759c4b8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/db566a849aa1/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/3878509eb009/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/27e54d25fbf4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/384902878115/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/021158b0b069/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/2c4ab6c2e4c2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/2e78cf86d105/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/c607d759c4b8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/db566a849aa1/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e0/8324995/3878509eb009/gr8.jpg

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