Liu Weihua, Liu Peiqinq, Tao Sha, Deng Yanhui, Li Xuejuan, Lan Tian, Zhang Xiaoyan, Guo Fenfen, Huang Wenge, Chen Fengying, Huang Heqing, Zhou Shu-Feng
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guagnzhou 510080, PR China.
Arch Biochem Biophys. 2008 Jul 15;475(2):128-34. doi: 10.1016/j.abb.2008.04.022. Epub 2008 Apr 29.
Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus, is a major cause of end-stage renal disease. Berberine is one of the main constituents of Coptidis rhizoma and Cortex phellodendri. In the present study, we examined effects of berberine (BBR) on renal injury in streptozotocin-induced diabetic rats, and on the changes of aldose reductase (AR) and oxidative stress in cultured rat mesangial cells exposed to high glucose. Fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were detected by using the commercially available kits. Cell proliferation, collagen synthesis, aldose reductase (AR), superoxide anion, superoxide dismutase (SOD), and malondialdehyde (MDA) were detected, respectively, by different methods. In streptozotocin-induced diabetic rats, fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were significantly decreased in rats treated with 200 mg/kg berberine for 12 weeks compared with diabetic control rats (P < 0.05). This was accompanied by a reduced AR activity and gene expression at both mRNA and protein levels. In cultured rat mesangial cells exposed to high glucose, incubation of BBR significantly decreased cell proliferation, collagen synthesis and AR activity as well as its mRNA and protein levels compared with control cells (P < 0.05). In vitro, BBR also significantly increased SOD activity and decreased superoxide anion and MDA compared with control cells (P < 0.05). These results suggested that BBR could ameliorate renal dysfunction in DN rats, which may be ascribed to inhibition of AR in mesangium, reduction of oxidative stress, and amelioration of extracellular matrix synthesis and cell proliferation. Further studies are warranted to explore the role of AR in DN and the therapeutic implications by AR inhibitors such as BBR.
糖尿病肾病（DN）是糖尿病最严重的微血管并发症之一，是终末期肾病的主要病因。黄连素是黄连和黄柏的主要成分之一。在本研究中，我们研究了黄连素（BBR）对链脲佐菌素诱导的糖尿病大鼠肾损伤的影响，以及对高糖培养的大鼠系膜细胞中醛糖还原酶（AR）和氧化应激变化的影响。使用市售试剂盒检测空腹血糖、血尿素氮、肌酐和24小时尿蛋白。分别采用不同方法检测细胞增殖、胶原合成、醛糖还原酶（AR）、超氧阴离子、超氧化物歧化酶（SOD）和丙二醛（MDA）。在链脲佐菌素诱导的糖尿病大鼠中，与糖尿病对照大鼠相比，用200mg/kg黄连素治疗12周的大鼠空腹血糖、血尿素氮、肌酐和24小时尿蛋白显著降低（P<0.05）。这伴随着AR活性以及mRNA和蛋白质水平的基因表达降低。在高糖培养的大鼠系膜细胞中，与对照细胞相比，BBR孵育显著降低细胞增殖、胶原合成和AR活性以及其mRNA和蛋白质水平（P<0.05）。在体外，与对照细胞相比，BBR还显著增加SOD活性并降低超氧阴离子和MDA（P<0.05）。这些结果表明，BBR可以改善DN大鼠的肾功能障碍，这可能归因于对系膜中AR的抑制、氧化应激的降低以及细胞外基质合成和细胞增殖的改善。有必要进一步研究AR在DN中的作用以及BBR等AR抑制剂的治疗意义。
