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隐丹参酮通过调节 STAT5 在大鼠模型中对缺血性中风具有治疗作用。

Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model.

机构信息

Department of Rehabilitation, Jinhua Central Hospital, Jinhua City, P.R. China.

出版信息

Pharm Biol. 2021 Dec;59(1):465-471. doi: 10.1080/13880209.2021.1914672.

DOI:10.1080/13880209.2021.1914672
PMID:33915069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8871624/
Abstract

CONTEXT

Cryptotanshinone (CT), a lipophilic compound extracted from roots of Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear.

OBJECTIVE

This study examines the effect of CT on ischaemic stroke.

MATERIALS AND METHODS

We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g,  = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group.

RESULTS

The 50% inhibitory concentration (IC) of CT on CD4 cell damage was 485.1 μg/mL, and median effective concentration (EC) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4CD25FOXP3 Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4CD25 Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4 T cells of the MCAO model.

DISCUSSION AND CONCLUSION

Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.

摘要

背景

隐丹参酮(CT)是一种从唇形科植物丹参的根中提取的脂溶性化合物,在多种疾病中具有多种特性,如肺纤维化、肺癌和骨关节炎。我们之前的研究结果表明,CT 在脑卒中有保护作用。然而,CT 在缺血性中风中的保护作用的分子机制尚不清楚。

目的

本研究探讨 CT 对缺血性中风的影响。

材料和方法

我们使用大脑中动脉闭塞(MCAO)大鼠(Sprague-Dawley 大鼠,200±20g,n=5)模型,假手术组作为阴性对照。MCAO 大鼠用 15mg/kg CT 灌胃给药。此外,用 TGF-β(5ng/mL)处理 MCAO 大鼠作为阳性对照组。

结果

CT 对 CD4 细胞损伤的 50%抑制浓度(IC)为 485.1μg/ml,中效浓度(EC)为 485.1μg/ml。CT 可减轻 MCAO 模型中的梗死区域。MCAO 组外周血中 CD4CD25FOXP3 Treg 细胞的比例随着 CT 治疗而增加。CT 可恢复模型组 CD4CD25 Treg 细胞中 FOXP3 蛋白水平和 STAT5 的磷酸化。重要的是,用 CD4 T 细胞中的 STAT5-IN-1 抑制剂处理可阻断 CT 治疗对 MCAO 模型的作用。

讨论与结论

我们的研究结果不仅增强了对 CT 治疗机制的理解,还表明其作为缺血性中风治疗有潜力的药物的潜在价值。进一步的研究对于检查 CT 对缺血性中风患者的影响将是有价值的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/3f14fb4411d8/IPHB_A_1914672_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/d6175ec2b789/IPHB_A_1914672_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/fd3285a0f8bf/IPHB_A_1914672_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/1d1ab89c6b89/IPHB_A_1914672_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/60ad50d4d96a/IPHB_A_1914672_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/3f14fb4411d8/IPHB_A_1914672_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/d6175ec2b789/IPHB_A_1914672_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/fd3285a0f8bf/IPHB_A_1914672_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/1d1ab89c6b89/IPHB_A_1914672_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/60ad50d4d96a/IPHB_A_1914672_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e72/8871624/3f14fb4411d8/IPHB_A_1914672_F0005_B.jpg

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