姜黄素抗草酸钙结晶致大鼠肾损伤的机制研究

目的 探讨姜黄素对大鼠肾草酸钙结晶肾损伤的影响及可能机制。 方法 40只C57BL/6大鼠随机分为5组:模型组(乙醛酸盐100 mg·kg^-1·d^-1)、不同剂量姜黄素(20,40,60 mg·kg^-1·d^-1)干预组和空白对照组。干预4周后检测各组大鼠的血、尿生化指标,肾脏结晶,大鼠肾脏丙二醛(MDA)含量和血红素加氧酶-1(HO-1)活性等指标; Western-blot检测各组大鼠肾组织中的核因子E2相关因子-2(NRF-2)和HO-1蛋白的表达含量。 结果 模型组大鼠的尿离子钙和尿草酸浓度分别为(3.37±0.13)和(2.50±0.05)mmol/L,相较于空白对照组大鼠(2.27±0.17)和(2.04±0.05)mmol/L]显著升高(P<0.05); 模型组大鼠血清肌酐(SCr)水平、肾脏MDA含量、肾脏结晶及肾小管上皮细胞凋亡指数与空白对照组比较均显著升高(P<0.05)。随着姜黄素干预剂量的增加,大鼠的SCr和肾脏MDA含量呈下降趋势、肾脏结晶和肾小管上皮细胞凋亡指数有减轻趋势,与模型组比较,差别有统计学意义(P<0.05); 而肾脏HO-1活性程度、NRF-2蛋白和HO-1蛋白表达均呈升高趋势,与模型组比较,差别有统计学意义(P<0.05)。 结论 姜黄素可减轻大鼠草酸钙结晶引起的氧化应激肾损伤,减少草酸钙结晶形成,该作用可能与其上调NRF-2/HO-1蛋白表达有关。

Investigation of the Protective Effect of Curcumine on Crystallization of Calcium Oxalate-Induced Kidney Injury in Rat

Objective To study the effects and mechanisms of curcumine on rat kidney injury induced by crystallization of calcium oxalate. Methods Forty C57BL/6 rats were randomly divided into five groups: pure crystalline group(given 100 mg/kg glyoxylate), the curcumine intervention groups(given 100 mg/kg glyoxylate and different concentration of curcumine: 20, 40 and 60 mg·kg^-1·d^-1), and control group, with 8 rats in each group. After 4 weeks of the intervention, the biochemical indicators in blood and urine, the degree of kidney damage and the crystallinity of rat kidney of each group were analyzed and observed; the content of malondialdehyde(MDA)and the activity of HO-1 in each renal tissue were detected; Western-blot was employed to detect the expression of NRF-2 and HO-1 in renal tissue.Results Compared with the control group, the level of urine calcium(3.37±0.13)and oxalate(2.50±0.05)mmol/L in model group were significantly increased(P<0.05). The concentration of SCr, the content of MDA, the degree crystallinity of rat kidney, and the apoptotic index of renal tubular epithelial cell in the model group were significantly higher than those in the control group(P<0.05). In the curcumine intervention groups,the level of urine calcium and oxalate, the content of MDA, the degree crystallinity of rat kidney, and the apoptotic index renal tubular epithelial cell in each group were decreased with increase of curcumine dosage, and compared with model group, the difference was statistically significant(P<0.05). The activity of HO-1, the expression of NRF-2, and HO-1 were increased, compared with model group, the difference was statistically significant(P<0.05). Conclusion Curcumine has effect on relieving oxidative stress and kidney injury caused by calcium oxalate crystallization, and reducing calcium oxalate crystal formation, which may be related to the increase of NRF-2 /HO-1 protein expression.