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提取物通过 TLR4/NF-kB 通路预防 Apoe-/- 小鼠早期动脉粥样硬化的发生。

Extract Prevents the Occurrence of Early Atherosclerosis in Apoe -/- Mice via TLR4/ NF-kB Pathway.

机构信息

Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.

Scientific Research Center, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.

出版信息

Cardiovasc Hematol Agents Med Chem. 2023;21(3):232-239. doi: 10.2174/1871525721666230206112134.

Abstract

OBJECTIVE

(SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), A mixture of these four ingredients is called SABP. Although aqueous extract from has been traditionally used to treat cardiovascular diseases, the efficacy and function of the optimal ratio of SABP in preventing and treating cardiovascular diseases remain unknown. This study aims to explore the antiinflammatory mechanisms underlying the attenuation of atherosclerosis development by aqueous extract from .

METHODS

Male ApoE mice (6 weeks) were randomly allocated into three groups: the model group (Model), the SABP group (SABP), and the rosuvastatin calcium group (RC). Male C57BL/6 mice (6 weeks) were used as a control group. All mice were fed with an ordinary diet. After 8 weeks of treatment, the lipid profiles in serum and the lactate dehydrogenase (LDH) and creatine kinase (CK) in heart tissue were measured using an automatic biochemical analyzer. Alterations of the thoracic aorta and the heart were assessed using Hematoxylin and eosin staining. The protein expression of Toll-like receptor 4 (TLR4), TGF beta-activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the heart tissue were determined though immunohistochemistry and western blotting analysis.

RESULTS

The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels were increased, and the high-density lipoprotein cholesterol (HDL-C) level was decreased in ApoE mice. SABP significantly decreased serum lipid levels and improved histopathology in the thoracic aorta. In addition. SABP treatment inhibited the expression of TLR4, TAK1, NF-κB, IL-6 and TNF-α in the heart in ApoE mice. The LDH and CK in the heart did not differ significantly among different groups, and the heart did not have obvious pathological changes.

CONCLUSION

These findings indicated that SABP may exert an anti-atherosclerotic effect by lowering blood lipids and inhibiting inflammatory response via TLR4/ NF-κB signaling pathway.

摘要

目的

(SM)含有四种主要的水溶性活性成分,它们已被分离、纯化和鉴定为丹参素(DSS)、丹酚酸 A(Sal-A)、丹酚酸 B(Sal-B)和原儿茶醛(PAL),这四种成分的混合物称为 SABP。虽然传统上使用 的水提物治疗心血管疾病,但预防和治疗心血管疾病的 SABP 最佳比例的功效和功能仍不清楚。本研究旨在探讨水提物减轻动脉粥样硬化发展的抗炎机制。

方法

雄性 ApoE 小鼠(6 周)随机分为三组:模型组(Model)、SABP 组(SABP)和瑞舒伐他汀钙组(RC)。雄性 C57BL/6 小鼠(6 周)作为对照组。所有小鼠均喂食普通饮食。治疗 8 周后,使用自动生化分析仪测量血清中的血脂谱以及心脏组织中的乳酸脱氢酶(LDH)和肌酸激酶(CK)。使用苏木精和伊红染色评估胸主动脉和心脏的变化。通过免疫组织化学和 Western blot 分析测定心脏组织中 Toll 样受体 4(TLR4)、TGF beta 激活激酶 1(TAK1)、核因子 kappa-B(NF-κB)、白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)的蛋白表达。

结果

ApoE 小鼠的血清低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和总胆固醇(TC)水平升高,高密度脂蛋白胆固醇(HDL-C)水平降低。SABP 可显著降低血清脂质水平并改善胸主动脉的组织病理学。此外,SABP 治疗抑制了 ApoE 小鼠心脏中 TLR4、TAK1、NF-κB、IL-6 和 TNF-α 的表达。不同组间心脏的 LDH 和 CK 无明显差异,心脏无明显病理改变。

结论

这些发现表明,SABP 通过降低血脂和抑制 TLR4/NF-κB 信号通路的炎症反应,可能发挥抗动脉粥样硬化作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2718/10258915/dff4dbea8faa/CHAMC-21-232_F1.jpg

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