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Archive > Volume 15 Issue 4 > 2023,15(4):556-563. DOI:https://doi.org/10.1016/j.chmed.2022.12.008 Prev Next

芒果苷通過(guò)抑制MCP-1/CCR2信號(hào)通路減輕自發(fā)性高血壓大鼠腎臟炎癥損傷

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

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    摘要:
    目的：高血壓是一種低度炎癥狀態(tài)的疾病，易并發(fā)腎臟炎癥反應(yīng)。芒果苷(Mangifera indica)是包括芒果在內(nèi)的多種植物中的一種藥理活性化合物，具有很強(qiáng)的抗炎活性。然而，MGF對(duì)自發(fā)性高血壓大鼠(SHR)腎炎癥損傷的影響尚不清楚。本研究旨在探討MGF對(duì)SHR腎炎性損傷的保護(hù)作用及其機(jī)制。 方法：MGF以10、20、40 mg/kg/d的劑量連續(xù)給藥8周。采集血液和尿液評(píng)估腎功能。采集腎臟組織進(jìn)行組織學(xué)、免疫組化、ELISA、Western blot和實(shí)時(shí)逆轉(zhuǎn)錄PCR (RT-PCR)分析。 結(jié)果：SHR中白細(xì)胞介素6(IL-6)、腫瘤壞死因子-α(TNF-α)、單核細(xì)胞趨化蛋白-1(MCP-1)和重組趨化因子C-C-Motif受體2 (CCR2)水平升高，IL-10水平降低。MGF可抑制IL-6、TNF-α、MCP-1和CCR2的表達(dá)，促進(jìn)IL-10的表達(dá)。模型組大鼠血尿素氮(BUN)含量和血清尿酸(SUA)含量均顯著升高，MGF對(duì)這些參數(shù)在各劑量水平均無(wú)明顯影響。 結(jié)論:本研究證實(shí)SHR腎臟存在明顯的炎癥損傷，MGF對(duì)SHR腎臟炎癥損傷具有保護(hù)作用;保護(hù)機(jī)制可能部分由MCP-1/CCR2信號(hào)通路介導(dǎo)。因此，它是一種潛在的治療高血壓的新藥。

    Abstract:
    Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys’ inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

    關(guān)鍵詞:
    高血壓;芒果苷;MCP-1 / CCR2;腎炎性損傷;自發(fā)性高血壓大鼠

    Keywords:


    Project Supported:
    The present study was supported by Natural Science Foundation of Guangxi Province (No. 2013GXNSFAA019114) and Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica Project (No. 12-071-08).

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