灯盏花乙素调节RhoA/ROCK信号通路对糖尿病肾病大鼠肾组织损伤的影响

doi:10.3969/j.issn.1006-6233.2023.05.04

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摘要 目的:探讨灯盏花乙素(Scu)调节RhoA/ROCK信号通路对糖尿病肾病(DN)大鼠肾组织损伤的影响。方法:将SD大鼠随机选择10只作为对照组(Con),其余60大鼠构建DN模型,造模成功的大鼠按随机数字表法分为5组:DN组、Scu低剂量组(Scu-L组,25mg/kg)、Scu中剂量组(Scu-M组,50mg/kg)、Scu高剂量组(Scu-H组,100mg/kg)、Scu-H+LPA组(100mg/kg Scu+50μmoL/L的RhoA/ROCK信号通路激活剂LPA)。ELISA试剂盒法检测24h尿微量白蛋白(MAU)及血清生化指标;HE染色、Masson染色观察肾组织损伤情况;RT-qPCR及Western blot检测TGF-β1、VEGF、PTEN水平;Western blot检测RhoA/ROCK通路蛋白水平。结果:Con组大鼠肾小球形态结构正常;DN组肾小球形态结构异常,肾小管出现水肿以及坏死现象,鲍曼囊出现粘连现象且出现大面积的蓝染胶原纤维沉积;Scu处理后,肾小管水肿以及坏死现象减少,肾小球形态结构变得较为规则,鲍曼囊腔缩小,且蓝染胶原纤维沉积减小。与Con组相比,DN组FBG、BUN、Scr、MAU、IL-6、TNF-α、TGF-β1、VEGF mRNA及蛋白水平、RhoA、p-ROCK/ROCK蛋白水平均显著升高(P<0.05),PTEN mRNA及蛋白水平显著下降(P<0.05);Scu处理后,FBG、BUN、Scr、MAU、IL-6、TNF-α、TGF-β1、VEGF mRNA及蛋白水平、RhoA、p-ROCK/ROCK蛋白水平均显著下降(P<0.05),PTEN mRNA及蛋白水平显著升高(P<0.05),且Scu添加剂量越高,作用效果越明显;LPA消除了Scu-H组对DN大鼠的改善作用。结论:Scu可能通过下调RhoA/ROCK信号通路减轻DN大鼠肾组织损伤。

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关键词 ：灯盏花乙素, RhoA/ROCK信号通路, 糖尿病肾病

Abstract：Objective: To investigate the influence of scutellarin (Scu) on renal tissue damage in diabetic nephropathy (DN) rats by regulating RhoA/ROCK signaling pathway. Methods: Ten SD rats were randomly selected as the control group, and the rest of the 60 rats were constructed as DN models, the rats with successful modeling were grouped into 5 subgroups according to random number table method: DN group, Scu-L group (25mg/kg, 8 weeks), Scu-M group (50mg/kg, 8 weeks), Scu-H group (100mg/kg, 8 weeks), Scu-H+LPA group (100mg/kg Scu, 8 weeks+50μmol/L RhoA/ROCK signaling pathway activator LPA, 2 weeks). ELISA kit was used to detect 24h urine microalbumin (MAU) and serum biochemical indexes; HE staining and Masson staining were applied to observe kidney tissue damage; RT-qPCR and Western blot were applied to detect TGF-β1, VEGF, PTEN levels; Western blot was applied to detect RhoA/ROCK pathway protein levels. Results: The morphology and structure of the glomeruli in the Control group were normal; in the DN group, the glomerular morphology and structure were abnormal, the renal tubules appeared edema and necrosis, and the Bowman's capsule showed adhesion and large blue-stained collagen fiber deposits; after Scu treatment, renal tubular edema and necrosis were reduced, the morphology and structure of glomeruli became more regular, Bowman's cysts were reduced, and the deposition of blue-stained collagen fibers was decreased. Compared with the Con group, FBG, BUN, Scr, MAU, IL-6, TNF-α, TGF-β1, VEGF mRNA and protein levels, RhoA, p-ROCK/ROCK protein levels in the DN group were obviously increased (P<0.05), PTEN mRNA and protein levels were obviously decreased (P<0.05); after Scu treatment, FBG, BUN, Scr, MAU, IL-6, TNF-α, TGF-β1, VEGF mRNA and protein levels, RhoA, p-ROCK/ROCK protein levels were obviously decreased (P<0.05), PTEN mRNA and protein levels were obviously increased (P<0.05), and the higher the Scu additive dose, the more obvious the effect; LPA abolished the ameliorating effect of Scu-H group on DN rats. Conclusion: Scu may alleviate renal tissue damage in DN rats by down-regulating RhoA/ROCK signaling pathway.

Key words： Scutellarin RhoA/ROCK signaling pathway Diabetic nephropathy

基金资助:河北省邯郸市科学技术研究与发展计划项目,(编号:19422083009-30)

引用本文:

王静, 李敏, 何立明, 高瑞超, 檀增桓. 灯盏花乙素调节RhoA/ROCK信号通路对糖尿病肾病大鼠肾组织损伤的影响[J]. 河北医学, 2023, 29(5): 721-726.
WANG Jing, LI Min, HE Liming, et al. Influence of Scutellarin on Renal Tissue Damage in Rats with Diabetic Nephropathy by Regulating RhoA/ROCK Signaling Pathway. HeBei Med, 2023, 29(5): 721-726.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.05.04 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I5/721

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