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丹参醇通过促进 VLDLR 的表达来缓解溃疡性结肠炎。

Tanshinol alleviates ulcerative colitis by promoting the expression of VLDLR.

机构信息

Department of Anorectal Surgery, Wuxi Traditional Chinese Medicine Hospital, Wuxi, PR China.

Endoscopic Center, Wuxi YEBO Proctology Hospital of Traditional Chinese Medicine, Wuxi, PR China.

出版信息

Drug Dev Res. 2021 Dec;82(8):1258-1268. doi: 10.1002/ddr.21840. Epub 2021 Jun 18.

Abstract

Tanshinol (TAN) is a widely used Chinese medicine ingredient with anti-inflammatory activity. The therapeutic effect of TAN in ulcerative colitis (UC) deserves further investigation. DSS induced UC model for mice, and TAN of different concentrations was used for in vivo therapy. Colons length was measured; expression of VLDLR in colonic mucosal tissue was evaluated by qRT-PCR, Western blot and histochemical staining. Besides, normal colorectal mucosal cell line (FHC) was treated with LPS to imitate the inflammatory process of UC in vitro. Different concentrations of TAN treated UC cell model. ELISA and qRT-PCR were applied to examine the concentrations of inflammatory cytokines (TNF-α, IL-6, IL-8, or IL-1β). Flow cytometry and MTT was used to identify the apoptosis and viability of FHC cells, respectively. Afterwards, Western blot was performed to detect the expressions of Bax, Bcl-2, Cleaved caspase-3, and Cleaved caspase-9 in FHC cells. VLDLR was low-expressed in UC tissues as compared to the normal tissue. TAN could alleviate DSS-induced colons length shortening, colonic tissue structure destruction, inflammatory response, and VLDLR expression decrease in vivo. Further study found that TAN could alleviate LPS-induced inflammatory response, apoptosis, and viability decrease of FHC cells, and siVLDLR could partially offset the effect of TAN. TAN alleviates LPS-induced viability decrease, apoptosis, and inflammatory response in FHC cells by promoting VLDLR expression.

摘要

丹参酮(TAN)是一种具有抗炎活性的常用中药成分。TAN 在溃疡性结肠炎(UC)中的治疗效果值得进一步研究。本研究构建 DSS 诱导的 UC 模型小鼠,并进行体内治疗。测量结肠长度;通过 qRT-PCR、Western blot 和组织化学染色评估结肠黏膜组织中 VLDLR 的表达。此外,用 LPS 处理正常结直肠黏膜细胞系(FHC)模拟 UC 的炎症过程。用不同浓度的 TAN 处理 UC 细胞模型。应用 ELISA 和 qRT-PCR 检测炎症细胞因子(TNF-α、IL-6、IL-8 或 IL-1β)的浓度。流式细胞术和 MTT 分别用于鉴定 FHC 细胞的凋亡和活力。然后,通过 Western blot 检测 FHC 细胞中 Bax、Bcl-2、Cleaved caspase-3 和 Cleaved caspase-9 的表达。与正常组织相比,UC 组织中 VLDLR 表达降低。TAN 可减轻 DSS 诱导的结肠缩短、结肠组织结构破坏、体内炎症反应和 VLDLR 表达降低。进一步研究发现,TAN 可减轻 LPS 诱导的 FHC 细胞炎症反应、凋亡和活力下降,而 siVLDLR 可部分抵消 TAN 的作用。TAN 通过促进 VLDLR 表达减轻 LPS 诱导的 FHC 细胞活力下降、凋亡和炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/189e/9290650/9f076c455c2c/DDR-82-1258-g006.jpg

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