Effect of Shuangdan Mingmu Capsule on Diabetic Retinopathy in Rats via Regulation of miRNAs.
Effect of Shuangdan Mingmu Capsule on Diabetic Retinopathy in Rats via Regulation of miRNAs.
复制标题
双丹明目胶囊通过miRNA调控对大鼠糖尿病视网膜病变的影响
DOI：
10.2147/dmso.s379611
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Qin, Yuhui
中科院分区：
文献类型：
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作者：
Li, Xiang;Yang, Yijing;Song, Yan;Nie, Fujiao;Fu, Chaojun;Qin, Yuhui
目的探讨双单明目胶囊通过调节mirna对大鼠糖尿病视网膜病变的影响。材料与方法采用链脲佐菌素（STZ） 50 mg/kg成功诱导雄性sd大鼠糖尿病，将其随机分为服用SDMM胶囊组（“糖尿病+SDMM”组）、对照组（“糖尿病”组）和正常组（n=10/组）。糖尿病+SDMM胶囊组灌胃SDMM胶囊1.89g/kg/d，其余各组灌胃等量蒸馏水。灌胃12周后，取大鼠视网膜进行组织病理学分析，并进行miRNA测序实验，鉴定miRNA的差异表达。然后用实时定量聚合酶链反应（qRT-PCR）证实这些结果。结果SDMM胶囊改善了视网膜形态，恢复了神经节细胞层的细胞数量（p<0.0001），减少了视网膜各层的细胞凋亡（外核层、内核层和神经节细胞层的p值分别为0.0001、0.0147、0.0034）。此外，大鼠服用SDMM胶囊后，miRNA表达发生变化。与糖尿病组相比，糖尿病+SDMM胶囊组有6个mirna上调，4个mirna下调。qRT-PCR验证结果显示，miR-450b-5p、miR-1249、miR-155-5p的表达水平与miRNA测序结果趋势一致，且经SDMM胶囊处理后均上调表达。靶基因预测和京都基因与基因组百科全书（KEGG）差异表达miRNAs分析显示，这些途径主要集中在局灶黏着和PI3K/Akt、MAPK、神经因子信号通路。结论SDMM胶囊可能通过调节miR-450b-5p、miR-1249和miR-155-5p的表达来预防和治疗糖尿病视网膜病变。
Purpose To evaluate the effects of Shuangdan Mingmu (SDMM) capsule on diabetic retinopathy in rats by regulating miRNAs. Materials and Methods Streptozotocin (STZ) (50 mg/kg) was successfully used to induce diabetes in male Sprague-Dawley rats, which were randomly assigned to a group taking SDMM capsules (“diabetic+SDMM”) or a control group (“diabetic”), and the normal group (n=10/group). The diabetic+SDMM capsule group received 1.89g/kg/d of SDMM capsule by gavage, whereas the other groups received the same amount of distilled water. After 12-weeks of gavage, the retina was removed from all rats for histopathological analysis, and miRNA sequencing experiments were carried out to identify the differential expression of miRNAs. These results were then confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Results SDMM capsules improved retinal morphology, restored the number of cells in the ganglion cell layer (p<0.0001) and reduced apoptosis in all retinal layers (p values in the outer nuclear layers, inner nuclear layers and ganglion cell layers 0.0001, 0.0147, 0.0034, respectively). In addition, miRNA expression was changed in rats taking SDMM capsules. Compared with the diabetic group, six miRNAs were up-regulated and four miRNAs were down-regulated in the diabetic+SDMM capsule group. The qRT-PCR validation results showed that the expression levels of miR-450b-5p, miR-1249 and miR-155-5p were consistent with the trend of miRNA sequencing results, and were all up-regulated after SDMM capsule treatment. Target gene prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed miRNAs showed that these pathways were mainly concentrated in the focal adhesions and PI3K/Akt, MAPK, and neural factor signaling pathways. Conclusion SDMM capsules may prevent and treat diabetic retinopathy by regulating the expression of miR-450b-5p, miR-1249 and miR-155-5p.