法舒地尔对高糖培养肾小管上皮细胞增殖和纤维化的影响#br#

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Abstract Objective: To investigate the influence of fasudil on the proliferation and fibrosis of human renal tubular epithelial cells incubated with high glucose. Methods: HK-2 cells were divided into normal control group (D-glucose 5.5 mmol/L), high tension group (D-glucose 5.5 mmol/L+54.5 mmol/L mannitol), high glucose group (D-glucose 60 mmol/L), high glucose+fasudil treatment group (the concentrations of fasudil were 5, 10 and 20 μmol/L). Cell proliferation was assessed with MTT assay. Changes in the p-MYPT1-Thr853 were detected with co-immunoprecipitation assay. The expression of connective tissue growth factor (CTGF) was detected with western blot, the protein content of transforming growth factor-β1 (TGF-β1) and fibronectin (Fn) in the supernatant were detected by ELISA. Results: Compared with normal control group, cell proliferation and the expression of p-MYPT1-Thr853, TGF-β1, CTGF and Fn were significantly increased in high glucose group. Compared with high glucose group, cell proliferation and the expression of p-MYPT1-Thr853, TGF-β1, CTGF and Fn were significantly decreased in fasudil treatment group. Conclusion: Fasudil can inhibit high glucose-induced proliferation and fibrosis of HK-2 and it may produce effect through the inhibition of Rho kinase activity.

Key words： fasudil renal tubular epithelial cells fibrosis diabetic nephropathy

Received: 27 August 2013

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	GU Lingjia1
	NI Liansong2.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2014/V44/I10/723

[1]Wolf G. Molecular mechanisms of diabetic mesangial cell hypertrophy: a proliferation of novel factors[J]. J Am Soc Nephrol, 2002, 13(10): 2611-2613.
[2]Chou CH, Chuang LY, Lu CY, et al. Interaction between TGF-β and ACE2-Ang-(1-7)-Mas pathway in high glucose-cultured NRK-52E cells[J]. Mol Cell Endocrinol, 2013, 366(1): 21-30.
[3]Okada H, Kikuta T, Kobayashi T, et al. Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis[J]. J Am Soc Nephrol, 2005, 16(1): 133-143.
[4]Danesh FR, Sadeghi MM, Amro N, et al. 3-Hydroxy-3-meth-ylglutaryl CoA reductase inhibitors prevent high glucose-in-duced proliferation of mesangial cells via modulation of RhoGTPase/p21 signaling pathway: implications for diabetic ne-phropathy[J]. Proc Natl Acad Sci USA, 2002, 99(12): 8301-8305.
[5]Peng F, Wu D, Gao B, et al. RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease[J]. Diabetes, 2008,57(6): 1683-1692.
[6]马东蔚, 王秋月, 马小羽, 等. 法舒地尔通过Rho/ROCK信号通路对高糖培养人肾小球系膜细胞炎症反应及纤维化的影响[J]. 中华内科杂志, 2011, 50(7): 580-584.
[7]Kolavennu V, Zeng L, Peng H, et al. Targeting of RhoA/ROCK signaling ameliorates progression of diabetic ne-phropathy independent of glucose control[J]. Diabetes, 2008, 57(3): 714-723.
[8]Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure[J].Intern Med, 2004, 43(1): 9-17.
[9]Gu L, Gao Q, Ni L, et al. Fasudil inhibits epithelial-Myo-fibroblast transdifferentiation of human renal tubular epi-thelial HK-2 cells induced by high glucose[J]. Chem Pharm Bull, 2013, 61(7): 688-694.
[10]吴甘霖, 贾汝汉, 肖圣顺, 等. 贝尼地平对糖尿病大鼠肾脏保护作用的机制探讨[J]. 中华糖尿病杂志, 2010, 2(4): 281-285.
[11]Wettschureck N, Offermanns S. Rho/Rho-kinase mediated signaling in physiology and pathophysiology[J]. J Mol Med, 2002, 80(10): 629-638.
[12]Gojo A, Utsunomiya K, Taniguchi K, et al. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in strepto-zotocin-induced diabetic rats[J]. Eur J Pharmacol, 2007, 568(1-3): 242-247.
[13]Xie X, Peng J, Chang X, et al. Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy[J]. Mol Cell Endocrinol, 2013, 369(1-2): 86-97.
[14]Komers R, Oyama TT, Beard DR, et al. Rho kinase inhibi-tion protects kidneys from diabetic nephropathy without re-ducing blood pressure[J]. Kidney Int, 2011, 79(4): 432-442.
[15]Wu G, Tu Y, Jia R. The inﬂuence of fasudil on the epitheli-al-mesenchymal transdifferentiation of renal tubular epi-thelial cells from diabetic rats[J]. Biomed Pharmacother, 2010, 64 (2): 124-129.