芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤

doi:10.5246/jcps.2023.06.039

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (6): 460-472.DOI: 10.5246/jcps.2023.06.039

芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤

胡小勤¹^,³, 丁雪菲¹, 邓家刚¹^,², 郝二伟¹^,², 杜正彩¹^,², 周蓓¹^,², 曾学文¹^,³^,^*()

1. 广西中医药大学药学院, 广西南宁 530001
2. 广西中药药效研究重点实验室, 广西南宁 530001
3. 金华高等研究院, 浙江金华 321000

收稿日期:2022-11-12 修回日期:2022-12-20 接受日期:2023-01-07 出版日期:2023-07-01 发布日期:2023-07-01
通讯作者: 曾学文
作者简介:
+ Tel.: +86-15907813718, E-mail: 109829069@qq.com

Mangiferin alleviates cardiac inflammatory injury in spontaneously hypertensive rats by inhibiting the MCP-1/CCR2 signaling pathway

Xiaoqin Hu¹^,³, Xuefei Ding¹, Jiagang Deng¹^,², Erwei Hao¹^,², Zhengcai Du¹^,², Bei Zhou¹^,², Xuewen Zeng¹^,³^,^*()

1 College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, China
2 Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Nanning 530001, China
3 Jinhua Advanced Research Institute, Jinhua 321000, China

Received:2022-11-12 Revised:2022-12-20 Accepted:2023-01-07 Online:2023-07-01 Published:2023-07-01
Contact: Xuewen Zeng

摘要/Abstract

摘要：

高血压是一种低度炎症状态的疾病, 通常伴有心脏炎症。芒果苷(MGF)是一种天然糖基蒽酮, 具有很强的抗炎活性。然而, MGF对高血压患者心脏炎症损伤的作用尚不清楚。本文研究MGF对自发性高血压大鼠(SHRs)心脏炎症损伤的保护作用及其机制。采用10周龄雄性SHRs和10周龄正常雄性Wistar-Kyoto (WKY)大鼠, 对SHRs使用10、20、40 mg/kg剂量的MGF, 连续8周。测量其收缩压(SBP)水平, 采集心脏组织进行形态学、免疫组化、ELISA、western blot和实时反转录PCR分析。结果表明模型组大鼠收缩压水平均较对照组显著升高, SHRs自发升高收缩压水平, 各剂量MGF对收缩压水平无显著影响。模型组大鼠心脏组织形态学结果显示有明显的炎症性损伤, MGF对这种损伤有显著的抑制作用。同时, MGF显著抑制了SHRs IL-6和TNF-α含量的升高。此外, MGF还显著抑制了SHRs MCP-1、CCR2蛋白以及其mRNA表达的增加。研究表明MGF并不会降低SHRs大鼠的SBP水平, 但MGF对SHRs大鼠的心脏炎症损伤具有保护作用, 这可能是因为MGF部分抑制了MCP-1/CCR2信号通路表达的原因。

关键词: 一, 芒果苷, MCP-1/CCR2信号通路, 心脏

Abstract:

Hypertension is a low-grade inflammation state of the disease and often complicated by inflammation of the heart. Mangiferin (MGF), which is a natural glucosyl xanthone, has a strong anti-inflammatory activity. However, the effects of MGF on cardiac inflammatory injury in hypertension remain unclear. In the present study, we investigated the protective effects and mechanisms of MGF on cardiac inflammatory injury in spontaneously hypertensive rats (SHRs). Briefly, 10-week-old male SHRs and 10-week-old male normotensive Wistar-Kyoto (WKY) rats were used. MGF was used in SHRs at doses of 10, 20, and 40 mg/kg for 8 weeks consecutively. The systolic blood pressure (SBP) level was measured, and the cardiac tissues were collected for morphology, immunohistochemistry, ELISA, Western blotting analysis, and real-time reverse transcription PCR (RT-PCR) analysis. The results showed that the SBP level was increased significantly in the model group compared with the control group both before and after intragastric administration, the SHRs increased the SBP level spontaneously, and all doses of MGF showed no significant effect on the SBP level. Cardiac histomorphology showed that there was an apparent inflammatory injury in the model group. MGF significantly inhibited this injury. Meanwhile, MGF significantly inhibited the increased abundance of IL-6 and TNF-α in SHRs. Furthermore, MGF also significantly inhibited the increased expressions of MCP-1 and CCR2 at the protein and mRNA levels in SHRs. In conclusion, this study demonstrated that MGF did not decrease the SBP level of SHRs. However, MGF had a protective effect on cardiac inflammatory injury in SHRs, which might be mediated partly by inhibiting the expression of the MCP-1/CCR2 signaling pathway.

Key words: Mangiferin, MCP-1/CCR2 Signaling Pathway, Cardiac

Supporting:

胡小勤, 丁雪菲, 邓家刚, 郝二伟, 杜正彩, 周蓓, 曾学文. 芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤[J]. 中国药学(英文版), 2023, 32(6): 460-472.

Xiaoqin Hu, Xuefei Ding, Jiagang Deng, Erwei Hao, Zhengcai Du, Bei Zhou, Xuewen Zeng. Mangiferin alleviates cardiac inflammatory injury in spontaneously hypertensive rats by inhibiting the MCP-1/CCR2 signaling pathway[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(6): 460-472.

图/表 9

Figure 1. Chemical structure of mangiferin.

Table 1. SBP in various groups (mmHg).

Figure 2. Effect of MGF on morphological changes in cardiac tissues of SHRs. (A) Histopathological changes in cardiac tissues of SHRs (H&E, 200×); (B) Histopathological changes in cardiac tissues of SHRs (Masson, 200×). Panels 1–6 represent morphological changes in the control group, model group, benazepril group, 10 mg/kg MGF group, 20 mg/kg MGF group, and 40 mg/kg MGF group, respectively.

Figure 3. Effect of MGF on morphological changes in cardiac tissues of SHRs. Ultrastructural changes in cardiac tissues of SHRs (TEM, 8000×). Panels 1–4 represent morphological changes in the control group, model group, benazepril group, and 40 mg/kg MGF group, respectively.

Figure 4. Effect of MGF on IL-6 and TNF-α expressions in cardiac tissues of SHRs. (A) Immunohistochemical staining for the expressions of IL-6 and TNF-α; (B) Quantification of immunohistochemical staining analysis of IL-6 and TNF-α. Panels 1–6 in (A) represent protein expression in the control group, model group, benazepril group, 10 mg/kg MGF group, 20 mg/kg MGF group, and 40 mg/kg MGF group, respectively. All data were expressed as mean ± SD, n = 8. **P < 0.01 vs. the control group; ##P < 0.01 vs. the model group.

Table 2. Effect of MGF on IL-6 and TNF-α contents in cardiac tissues of SHRs (ng/L).

Figure 5. Effect of MGF on MCP-1 and CCR2 expressions in cardiac tissues of SHRs. (A) Representative MCP-1, CCR2 bands, and corresponding GAPDH bands; (B) Quantification of the Western blotting analysis of MCP-1 and CCR2 expressions. Panels 1–6 in (A) represent protein expression in the control group, model group, benazepril group, 10 mg/kg MGF group, 20 mg/kg MGF group, and 40 mg/kg MGF group, respectively. All data were expressed as mean ± SD, n = 8. *P < 0.05, **P < 0.01 vs. the control group; #P < 0.05, ##P < 0.01 vs. the model group.

Figure 6. Effect of MGF on MCP-1 and CCR2 mRNA expression. (A) The Amplification Plot of MCP-1, CCR2, and GAPDH mRNA; (B) The relative mRNA value of MCP-1 and CCR2, which was determined and normalized to GAPDH, and data were analyzed by the method of 2–ΔΔCt. All data were expressed as mean ± SD, n = 8. **P < 0.01 vs. the control group; #P < 0.05, ##P < 0.01 vs. the model group.

Figure 7. The Mechanism of MGF inhibiting the expression of MCP-1/CCR2 signal to suppress the monocyte secretion of IL-6 and TNF-α.

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芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤

Mangiferin alleviates cardiac inflammatory injury in spontaneously hypertensive rats by inhibiting the MCP-1/CCR2 signaling pathway

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