蛇床子素调节Mincle/Syk/NF-κB信号通路对肾病综合征大鼠的治疗作用

doi:10.3969/j.issn.1006-6233.2023.03.06

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摘要 目的: 探讨蛇床子素(OST)调节巨噬细胞诱导性C型凝集素样受体(Mincle)/脾脏酪氨酸激酶(Syk)/核因子κB(NF-κB)信号通路对肾病综合征(NS)大鼠的治疗作用。方法: 随机选择10只大鼠记为N组,其它大鼠构建NS模型,将建模成功的50只大鼠随机平分为NS组(模型组)、L-OST组(10mg/kg OST)、M-OST组(20mg/kg OST)、H-OST组(40mg/kg OST)、H-OST+TDB组(40mg/kg OST+50μg TDB/周),OST每天注射1次,连续治疗4周。ELISA法检测血清中炎性因子(IL-1β、IL-6、TNF-α)、氧化应激指标(SOD、MDA、LDH)、24h尿液中UP水平;通过全自动化学分析仪检测BUN、Scr水平;HE染色以及Masson染色检测肾脏病理变化;TUNEL染色检测肾脏细胞凋亡;Western blot检测collagen I、Ly6g、Ki-67、Mincle/Syk/NF-κB通路蛋白表达。结果: N组肾组织结构正常,染色清晰,NS组出现大量间质炎性细胞浸润、肾小管萎缩、大量空泡的现象,NS组较N组24h UP、Scr、BUN含量、IL-1β、IL-6、TNF-α、MDA、LDH水平、胶原容积分数、凋亡率、collagen I、Ly6g、Ki-67、Mincle、Syk、p-NF-κB/NF-κB蛋白水平均显著升高(P<0.05),SOD水平显著下降(P<0.05);与NS组相比,L-OST组、M-OST组、H-OST组均改善炎性细胞浸润、肾小管萎缩现象,24h UP、Scr、BUN含量、IL-1β、IL-6、TNF-α、MDA、LDH水平、胶原容积分数、凋亡率、collagen I、Ly6g、Ki-67、Mincle、Syk、p-NF-κB/NF-κB蛋白水平均显著下降(P<0.05),SOD水平显著升高(P<0.05),且H-OST组治疗效果最佳;TDB消除了OST对NS大鼠肾损伤的改善作用。结论: OST可能通过抑制Mincle/Syk/NF-κB信号通路减轻OST大鼠的肾损伤。

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关键词 ：蛇床子素, 肾病综合征, 巨噬细胞诱导性C型凝集素样受体, 脾脏酪氨酸激酶, 核因子κB

Abstract：Objective: To investigate the therapeutic effect of osthol (OST) on nephrotic syndrome (NS) in rats by regulating macrophage-inducible C-type lectin (Mincle)/spleen tyrosine kinase (Syk)/nuclear factor-κB (NF-κB) signal pathway. Methods: Ten rats were randomly selected and recorded as group N, and other rats were used to construct NS model. The 50 successfully modeled rats were randomly divided into NS group (model group), L-OST group (10 mg/kg OST), M-OST group (20 mg/kg OST), H-OST group (40 mg/kg OST), H-OST+TDB group (40 mg/kg OST+50 μg TDB/week). OST was injected once a day for 4 consecutive weeks. The levels of inflammatory factors (IL-1β, IL-6, TNF-α), oxidative stress indicators (SOD, MDA, LDH) in serum and UP in 24h urine were detected by ELISA; the levels of BUN and Scr was measured by automatic chemical analyzer; HE staining and Masson staining were used to detect the pathological changes of kidney; TUNEL staining was used to detect renal cell apoptosis; Western blot was used to detect the expression of collagen I, Ly6g, Ki-67, and Mincle/Syk/NF-κB pathway proteins. Results: In group N, the renal tissue structure was normal and the staining was clear. In NS group, a large number of interstitial inflammatory cells infiltrated, renal tubules atrophied, and a large number of vacuoles were observed, compared with group N, the contents of 24h UP, Scr, BUN, levels of IL-1β, IL-6, TNF-α, MDA, LDH, the collagen volume fraction, apoptosis rate, the levels of collagen I, Ly6g, Ki-67, Mincle, Syk, p-NF-κB/NF-κB proteins in NS group increased significantly (P<0.05), the level of SOD decreased significantly (P<0.05); compared with NS group, the inflammatory cell infiltration and renal tubule atrophy in the L-OST group, M-OST group and H-OST group were improved, the contents of 24h UP, Scr, BUN, levels of IL-1β, IL-6, TNF-α, MDA, LDH, the collagen volume fraction, apoptosis rate, the levels of collagen I, Ly6g, Ki-67, Mincle, Syk, p-NF-κB/NF-κB proteins decreased significantly (P<0.05), the level of SOD increased significantly (P<0.05), the treatment effect of H-OST group was the best; TDB eliminated the ameliorative effect of OST on renal injury in NS rats. Conclusion: OST may alleviate renal injury in OST rats by inhibiting the Mincle/Syk/NF-κB signal pathway.

Key words： Osthol Nephrotic syndrome Mincle Syk NF-κB

基金资助:湖北省武汉市卫生健康委医疗卫生科研项目,(编号:WX19C20)

引用本文:

何晓梅, 丁洁, 王艳芳, 程群芳, 封宝红. 蛇床子素调节Mincle/Syk/NF-κB信号通路对肾病综合征大鼠的治疗作用[J]. 河北医学, 2023, 29(3): 380-387.
HE Xiaomei, DING Jie, WANG Yanfang, et al. Therapeutic Effects of Osthol in Modulating Mincle/Syk/NF-κB Signaling Pathway in Rats with Nephrotic Syndrome. HeBei Med, 2023, 29(3): 380-387.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.03.06 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I3/380