苄达赖氨酸对大鼠糖尿病肾病的防治作用

摘要/Abstract

摘要： 目的: 在大鼠肾系膜细胞及整体大鼠上观察卞达赖氨酸(bendazac lysine,BDL)对糖尿病肾病(diabetic nephropathy,DN)的防治作用。方法: 大鼠肾系膜细胞分别在3 种浓度的BDL 中培养36 h 后,流式细胞仪测定细胞S 期百分率;RT-PCR 法测定转化生长因子(transforming growth factor β₁ ,TGF-β₁)mRNA水平;放免法测定细胞内Ⅳ型胶原和层粘蛋白含量;糖尿病模型大鼠灌胃3 种剂量的BDL 8 周后,亲和层析法测定大鼠血清糖化血红蛋白。结果: 高糖和H₂O₂ 可使S 期细胞百分数大幅度降低,TGF-β₁mRNA 相对含量、Ⅳ型胶原和层粘蛋白含量明显升高。低中高3 个浓度的BDL 皆可使S 期细胞比例分别有不同程度的升高;使TGF-β₁ mRNA 相对含量、Ⅳ型胶原和层粘蛋白含量显著降低。中高剂量的BDL可显著降低大鼠血清糖化血红蛋白,并明显改善其生理和精神状态。结论: BDL 升高大鼠肾系膜细胞的S 期百分数,降低TGF-β₁ mRNA、Ⅳ型胶原和层粘蛋白水平的作用与DN 密切相关,是潜在的DN 防治药物。

关键词: 卞达赖氨酸, 尿病性肾病变, 肾系膜细胞, 大鼠

Abstract: AIM: To investigate the protective effects of bendazac lysine (BDL) on diabetic nephropathy (DN) in vitro and in vivo experiments. METHODS: After rat mesangial cells were cultured in 3 concentrations of BDL for 36 h, the percentages of S phase of cells were determined by flowcytometry ;the transforming growth factor β₁(TGF-β₁ ) mRNA level was assayed by reverse transcription PCR;and two main components of extracellular matrix (ECM) , collagen Ⅳ and laminin, were determined by radioimmunoassay. Streptozotocin (STZ) induced diabetic rats were administered BDL at doses of 100, 200, 400 mg/kg for 8 weeks. The physical behavior andHbAlC levels of rats were observed. RESULTS: In the presence of high glucose and H₂O₂ , the percentages of S phase of cells were lowered, and TGF-β₁ mRNA level, collagen Ⅳ and laminin level were significantly increased. When compared with those in the high glucose group, the percentages of S phase of cells were significantly raised, and the levels of TGF-β₁mRNA, collagen Ⅳ and laminin were statistically decreased. The physical behavior of high BDL treated rats restored to be vibrant, vigorous and weight gaining, and the HbAlC level was significantly reduced. CONCLUSION: BDL has the protective effects against damage caused by DN, and is a potential drug candidate worth further study in preventing and treating DN.

Key words: bendazac lysine, diabetic nephropathy, mesangial cells, rats

中图分类号:

R965.2

印晓星, 张银娣, 余俊先, 张蓓, 沈建平, 邱俊. 苄达赖氨酸对大鼠糖尿病肾病的防治作用[J]. 中国临床药理学与治疗学, 2007, 12(5): 552-561.

YIN Xiao-xing, ZHANG Yin-di, YU Jun-xian, ZHANG Bei, SHEN Jian-ping, QIU Jun. Protective effects of bendazac lysine against development of diabetic nephropathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(5): 552-561.

参考文献

1 Cooper ME, Gilbert RE, EpsteinM.Pathophysiology of diabetic nephropathy[J].Metabolism, 1998;47:3-6.
2 Iglesias-De La Cruz MC, Ruiz-Torres P, Alcami J, et al.Hydrogen peroxide increases extracellular matrix mRNA through TGF-β in human mesangial cells[J].Kidney Int, 2001;59:87-95.
3 Oates PJ, Mylari BL.Aldose reductase inhibitors:therapeutic implications for diabetic complications[J].Expert Opin Investig Drugs, 1999 ;8:2095-2119.
4 Ishii H, Tada H, Isogai S.An aldose reductase inhibitor prevents glucose-induced increase in transforming growth factor-beta and protein kinase C activity in cultured human mesangial cells [J].Dialectologia, 1998 ;41:362-364.
5 Heidland A, Sebekova K, Schinzel R.Advanced glycation end products and the progressive course of renal disease[J].Am J Kidney Dis, 2001 ;38:S100-S106.
6 Kelly DJ, Cox AJ, TolcosM, et al.Attenuation of tubular apoptosis by blockade of the renin-angiotensin sy stem in diabetic Ren-2 rats[J].Kidney Int, 2002;61:31-39.
7 Haralson MA, Jacobson HR, Hoover RL.Collagen polymorphism in cultured rat kidney mesangial cells[J].Lab Invest, 1987;57:513-523.
8 Ardaillou N, Bellon G, Nivez MP, et al.Quantification of collagen synthesis by cultured human glomerular cells[J].Biochem Biophys Acta, 1989 ;991:445-452.
9 Ausiello DA, Kreisberg JI, Roy C, et al.Contraction of cultured rat glomerular cells of apparent mesangial origin after stimulation with angiotensin II and vasopression[J].J Clin Invest,1980;65:754-760.
10 Ayo SH, Radnik RA, Glass WF 2nd, et al.Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium[J].Am J Physiol, 1991;260:F185-F191.
11 Balfour JA, Clissold SP, Bendazac ly sin.A review of its pharmacological properties and therapeutic potential in the management of cataracts[J].Drugs, 1990;39:575-596.
12 Yin XX, Zhang YD, Wu HW, et al.Protective effects of bendazac lysine on early experimental diabetic nephropathy rats[J]. Acta Pharmacol Sin, 2005;26:721-728.
13 Miller NJ, Rice-Evans C, Davies MJ, et al.A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates[J].Clin Sci,1993 ;84:407-412.
14 Yu L, Qiu HX, Chen WY, et al.The relationship between advanced glycosylation end products and the extracellular matrix of aorta in diabetic rats[J].Chin J Arteriosclerosis, 1999;7:311-314.
15 Shankland SJ, Scholey JW, Ly H, et al.Expression of transforming growth factor-beta 1 during diabetic renal hypertrophy [J].Kidney Int, 1994;46:430-442.
16 Wolf G.Cell cycle regulation in diabetic nephropathy[J].Kidney Int Suppl, 2000;7:S59-66.
17 Jandeleit-Dahm K, Cao Z, Cox AJ, et al.Role of hyperlipidemia in progressive renal disease:focus on diabetic nephropathy[J].Kidney Int Suppl, 1999 ;71:S31-S36.
18 Montero A, Munger KA, Khan RZ, et al.F( 2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type Ⅰ diabetes[J].Kidney Int,2000 ;58:1963-1972.
19 汪建云, 印晓星.糖尿病肾病中转化生长因子-β1 信号转导与肾纤维化[J].中国临床药理学与治疗学, 2005;10:371-377.
20 KalousovaM, Zima T, Tesar V, et al.Advanced glycation end products in clinical nephrology[J].Kidney Blood Press Res, 2004 ;27:18-28.
21 Schmut O, Fellinger C, Hofmann H.Bendazac lysine:a protective substance against oxygen-free radicals.Recent developments in the pharmacological treatment of cataract[S].KuglerPublications Amsterdam, 1987;69-72.
22 Musci G., Silvestrini B.Mechanism of the scavenger-like activity of bendazac[J].Drugs Exp Clin Res, 1987;13:289-292.

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