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针刺通过 TGF-β/Smad 通路减轻肾间质纤维化。

Acupuncture attenuates renal interstitial fibrosis via the TGF‑β/Smad pathway.

机构信息

Acupuncture and Massage College, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.

Acupuncture and Massage Rehabilitation College, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2267-2275. doi: 10.3892/mmr.2019.10470. Epub 2019 Jul 4.

Abstract

Acupuncture is one of the most useful tools in complimentary medicine, and has demonstrated potential value for treating chronic renal failure (CRF). However, the underlying mechanisms for its therapeutic effect remain unknown. In the present study, the effects of acupuncture on renal interstitial fibrosis (RIF) were explored in a rabbit model of CRF. Rabbits were assigned to the following five groups: sham, model, losartan potassium (Posi), acupuncture (Acup) and acupuncture+inhibitor (Acup+Inhib) groups. The CRF rabbits were administered a drug or/and acupuncture on Shenshu, Mingmen and Pishu. The body weights, urine protein, serum creatinine (SCr) and blood urea nitrogen (BUN) levels of the rabbits were measured. Transforming growth factor β (TGF‑β), integrin‑linked kinase (ILK) and Smad3 expression were detected by qRT‑PCR. Tumor necrosis factor‑α (TNF‑α) and endothelial nitric oxide synthase (eNOS) expression were analyzed by western blot methods. The concentrations of TGF‑β, IL‑8, TNF‑α and IL‑1β in blood serum were detected using ELISA kits. In addition, pathological characteristics of the rabbit tissues were evaluated by H&E and Masson's trichrome staining methods, and TGF‑β expression was detected by immunohistochemistry (IHC) assays. Results showing decreased body weights and increased urine protein, SCr and BUN levels confirmed that the CRF model had been successfully constructed. It was also found that acupuncture significantly reduced the levels of TNF‑α, Smad3, ILK and TGF‑β expression, dramatically decreased the concentrations of TGF‑β, IL‑8, TNF‑α and IL‑1β in blood serum, and significantly increased eNOS expression in the CRF model rabbits by affecting the TGF‑β/Smad signaling pathway. In addition, it was demonstrated that acupuncture could relieve RIF by affecting the TGF‑β/Smad pathway. These observations indicate that acupuncture may be useful for treating CRF, and suggest the TGF‑β/Smad pathway as a target for CRF therapy.

摘要

针刺是补充医学中最有用的工具之一,已证明其对治疗慢性肾衰竭(CRF)具有潜在价值。然而,其治疗效果的潜在机制尚不清楚。在本研究中,在 CRF 兔模型中探索了针刺对肾间质纤维化(RIF)的影响。将兔子分为以下五组:假手术组、模型组、氯沙坦钾组(Posi)、针刺组(Acup)和针刺+抑制剂组(Acup+Inhib)。CRF 兔给予药物和/或针刺肾俞、命门和脾俞。测量兔子的体重、尿蛋白、血清肌酐(SCr)和血尿素氮(BUN)水平。通过 qRT-PCR 检测转化生长因子β(TGF-β)、整合素连接激酶(ILK)和 Smad3 的表达。通过 Western blot 方法分析肿瘤坏死因子-α(TNF-α)和内皮型一氧化氮合酶(eNOS)的表达。采用 ELISA 试剂盒检测血清中 TGF-β、IL-8、TNF-α和 IL-1β的浓度。此外,通过 H&E 和 Masson 三色染色法评估兔组织的病理特征,并通过免疫组织化学(IHC)法检测 TGF-β的表达。结果显示,体重减轻,尿蛋白、SCr 和 BUN 水平升高,证实 CRF 模型构建成功。还发现针刺显著降低了 TNF-α、Smad3、ILK 和 TGF-β 的表达水平,显著降低了血清中 TGF-β、IL-8、TNF-α和 IL-1β的浓度,并通过影响 TGF-β/Smad 信号通路显著增加了 CRF 模型兔的 eNOS 表达。此外,研究表明针刺可以通过影响 TGF-β/Smad 通路来缓解 RIF。这些观察结果表明,针刺可能对治疗 CRF 有用,并提示 TGF-β/Smad 通路可能是 CRF 治疗的靶点。

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