摘要
目的探讨白藜芦醇(Res)对大鼠肾草酸钙结石形成的影响及与全蛋白Kelch样ECH相关蛋白1(Keap1)-核因子E2相关因子2(Nrf2)/血红素氧合酶1(HO-1)信号通路的关系。方法将60只雄性SD大鼠随机分成对照组、模型组、Res低剂量组(L-Res组)、Res高剂量组(H-Res组)和Res高剂量联合Nrf2抑制剂ML385组(H-Res+ML385组),每组12只。除对照组外,其他各组均采用1%乙二醇+2%氯化铵诱导法制备肾草酸钙结石模型,连续造模4周。造模的同时分别给予Res或联合ML385处理,连续给药4周。实验结束时,测定各组大鼠24 h尿量、尿pH值,尿Ca^2+浓度、尿草酸(Ox)含量以及血清尿氮素(BUN)、肌酐(Cr)、Ca^2+含量;取肾脏组织,检测肾脏组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性及活性氧(ROS)水平;Von Kossa染色观察大鼠肾脏组织草酸钙晶体形成情况;Western blot检测大鼠肾脏组织中核蛋白Nrf2及全蛋白Keap1、HO-1等表达。结果 Res可抑制模型大鼠肾脏组织中草酸钙晶体的形成,改善大鼠尿液、血液相关指标,降低肾脏组织中ROS水平和MDA含量,同时提高SOD活性,并可上调肾脏组织细胞核蛋白Nrf2及全蛋白Keap1和NO-1等蛋白的表达水平。然而,联合Nrf2抑制剂ML385处理则可抑制Res的作用效果。结论 Res可能通过激活Keap1-Nrf2/HO-1信号通路改善肾脏组织的氧化损伤,从而抑制大鼠肾脏组织草酸钙晶体的形成,具有预防肾结石的作用。
Objective To investigate the effect of resveratrol(Res) on the formation of renal calcium oxalate stone in rats and its relationship with Keap1-Nrf2/HO-1 signaling pathway. Methods Sixty male SD rats were randomly divided into five groups including control group, model group, Res low dose group(L-Res group), Res high dose group(H-Res group) and Res high dose combined with Nrf2 inhibitor ML385 group(H-Res+ML385), with 12 rats in each group. Except for control group, the other groups were given 1% ethylene glycol+2% ammonium chloride to establish kidney stones model for 4 weeks. Meanwhile, the rats were administered with resveratrol or combined with ML385 for 4 weeks. At the end of the experiment, the 24 h urine volume, urine pH, urine Ca^2+ concentration, uric acid(Ox) content and the serum of urinary nitrogen(BUN), creatinine(Cr) and Ca^2+ contents were measured in each group. The kidney tissues in each group were obtained and the content of malondialdehyde(MDA) content, activity of superoxide dismutase(SOD) and levels of reactive oxygen species(ROS) in kidney tissues were determined. The formation of calcium oxalate crystals in rat kidney tissue were observed using Von Kossa staining. The proteins expression of nucleus protein Nrf2 and whole proteins Keap1, HO-1 in kidney tissue of rats were detected by Western blot analysis. Results Resveratrol inhibited the formation of calcium oxalate crystals in the kidney tissue of rats, improved the indexes of urine and blood, reduced the levels of ROS and the content of MDA in kidney tissues, increased the activity of SOD, and up-regulated the proteins expression levels of nucleus protein Nrf2 and whole proteins Keap1, HO-1 in kidney tissues. However, combination treatment with Nrf2 inhibitor ML385 significantly inhibit the effects of resveratrol. Conclusion Resveratrol may be inhibit the oxidative damage of kidney tissue by activating Keap1-Nrf2/HO-1 signaling pathway, thereby inhibiting the formation of calcium oxalate crystals in rat kidney tissue, and has the effect of preventing kidney stones.
作者
邸彦橙
王志龙
张智慧
宋静
高强
吴影
南锡浩
郭振海
田河
Di Yancheng;Wang Zhilong;Zhang Zhihui(Dept of Urology,Hongqi Hospital Affiliated to Mudanjiang Medical University,Mudanjiang 157011;The First Clinical Medical College of Mudanjiang Medical University,Mudanjiang 157011)
出处
《安徽医科大学学报》
CAS
北大核心
2020年第1期70-74,共5页
Acta Universitatis Medicinalis Anhui
基金
黑龙江省卫生计生委科研课题(编号:2018370)
红旗科研基金科技项目(编号:2018HQ-18)
