大麻素受体1拮抗剂ZH-101-S对糖尿病大鼠肾脏的保护作用

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摘要 目的: 探讨新型大麻素受体1拮抗剂ZH-101-S对糖尿病大鼠肾脏的作用及机制。方法: 通过腹腔注射链脲佐菌素建立糖尿病大鼠模型，随机分为糖尿病组和低、中、高剂量组，每组6只，低、中、高剂量组分别于每天腹腔注射0.3，1.0，3.0 mg/kg ZH-101-S，另以健康大鼠作为对照组，对照组和糖尿病组腹腔注射等量生理盐水，8周后检测各组大鼠血尿素氮、血肌酐和尿白蛋白排泄率(urine albumin excretion rate, UAER)，测定肾组织丙二醛含量和超氧化物歧化酶(SOD)活力，HE染色观察肾组织病理改变，免疫印迹法检测肾组织细胞电压依赖性离子通道(voltage-dependent anion channel, VDAC)蛋白的表达。结果：与对照组比较，糖尿病组大鼠血肌酐、血尿素氮和UAER明显增高；肾组织SOD活性降低，丙二醛含量升高(P<0.05)；肾组织细胞VDAC表达明显降低(P<0.01)；肾小球体积增大，肾小管上皮细胞水肿，系膜基质增多。与糖尿病组比较，高剂量组大鼠UAER、血肌酐和血尿素氮明显降低；肾组织SOD活性明显升高，丙二醛含量明显降低；肾脏细胞VDAC表达增加(P<0.05)；肾组织病理形态得到一定改善。结论： ZH-101-S对糖尿病肾病大鼠肾脏具有保护作用，可能与抑制氧化应激和改善肾脏线粒体功能有关。

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关键词 ：大麻素受体, 拮抗剂, 糖尿病肾病, 氧化应激, 电压依赖性离子通道

Abstract：Objective： To investigate the protective effect of novel cannabinoid(CB) 1 receptor antagonist ZH-101-S on kidneys in streptozotocin induced diabetic rats. Methods：Diabetic models were established by intraperitoneal injection of streptozotocin, rats were randomized into diabetes mellitus group(DM group, normal saline, i.p.), low dose group(0.3 mg/kg ZH-101-S, i.p.), middle dose group(1.0 mg/kg ZH-101-S, i.p.), and high dose group(3.0 mg/kg ZH101S, i.p.); and healthy rats were selected as control group(normal saline, i.p.). After 8 weeks, the serum urea nitrogen(BUN), serum creatinine(Scr), urine albumin excretion rate(UAER), and the level of malondialdehyde(MDA) and the activity of superoxide dismutase(SOD) in renal tissues were detected; the pathological changes of renal tissues were observed by HE staining; the expression of voltage-dependent anion channel(VDAC) protein in renal tissues were examined by Western blotting. Results：Compared with control group, DM group showed higher levels of UAER, Scr and BUN(P<0.05), decreased SOD activity(P<0.01), and increased expression of MDA(P<0.05); decreased VDAC expression(P<0.01); glomerular volume increased, renal tubular epithelial cell edema, mesangial matrix increased. Compared with DM group, high dose group had lower levels of UAER, Scr and BUN, increased SOD activity, lower content of malondialdehyde; increased VDAC expression(P<0.01), the pathological morphology of the kidney was improved. Conclusion：ZH-101-S showed protective effect on the kidney of diabetic rats, which may be related to the inhibition of oxidative stress and the improvement of kidney mitochondrial function.

收稿日期: 2016-03-11

基金资助:

镇江市社会发展项目(SH2012038)

通讯作者: 吴晨光(通讯作者)，主任医师，E-mail: wcgzj1128@aliyun.com

作者简介: 邹昭(1989—)，男，硕士，湖北武汉人，住院医师，主要从事糖尿病肾病的研究；

引用本文:

邹昭，吴晨光，姜惠，等. 大麻素受体1拮抗剂ZH-101-S对糖尿病大鼠肾脏的保护作用[J]. 江苏大学学报:医学版, 2016, 26(05): 387-390. ZOU Zhao, WU Chen-guang, JIANG Hui. Protective effect of novel CB1 receptor antagonist ZH-101-S on renal function in diabetic rats. Journal of Jiangsu University(Medicine Edition), 2016, 26(05): 387-390.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2016/V26/I05/387

［1］李敏州, 高彦彬, 马鸣飞, 等. 糖尿病肾病发病机制研究进展\[J\]. 中国实验方剂学杂志, 2012, 18(22): 344-349.
［2］Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades\[J\]. Chem Biol Interact, 2009, 181(3): 297-308.
［3］Baines CP, Kaiser RA, Sheiko T, et al. Voltagedependent anion channels are dispensable for mitochondrialdependent cell death\[J\]. Nat Cell Biol, 2007, 9(5): 550-555.

［4］Wang L, Wu CG, Fang CQ, et al. The protective effect of αLipoic acid on mitochondria in the kidney of diabetic rats\[J\]. Int J Clin Exp Med, 2013, 6(2):90-97.
［5］Kunz I, Meier MK, Bourson A, et al. Effects of rimonabant, a cannabinoid CB1 receptor ligand, on energy expenditure in lean rats\[J\]. Int J Obes (Lond), 2008, 32(5):863-870.
［6］Nam DH, Lee MH, Kim JE, et al. Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice\[J\]. Endocrinology, 2012, 153(3):1387-1396.
［7］Barutta F, Corbelli A, Mastrocola R, et al. Cannabinoid receptor 1 blockade ameliorates albuminuria in experimental diabetic nephropathy\[J\]. Diabetes, 2010, 59(4): 1046-1054.
［8］Brownlee M. Biochemistry and molecular cell biology of diabetic complications\[J\]. Nature, 2001, 414(6865): 813-820.
［9］ShoshanBarmatz V, De Pinto V, Zweckstetter M, et al. VDAC, a multifunctional mitochondrial protein regulating cell life and death\[J\]. Mol Aspects Med, 2010, 31(3): 227-285.
［10］Orrenius S, Gogvadze V, Zhivotovsky B. Mitochondrial oxidative stress: implications for cell death\[J\]. Annu Rev Pharmacol Toxicol, 2007, 47: 143-183.
［11］Han D, Antunes FR, Rettori D, et al. Voltagedependent anion channels control the release of the superoxide anion from mitochondria to cytosol\[J\]. J Biol Chem, 2003, 278(8): 5557-5563.
［12］Janiak P, Poirier B, Bidouard JP, et al. Blockade of cannabinoid CB1 receptor improves renal function, metabolic profile, and increased survival of obese Zucker rats\[J\]. Kidney Int， 2007, 72(11): 1345-1357.