【摘要】 目的:探讨丁苯酞延缓梗阻性肾病小鼠肾脏纤维化的可能机制。方法:雄性小鼠分为假手术组(Sham)、模型组(UUO)、对照组(ACEI)及治疗组(NBP)。对照组、治疗组分别给予贝那普利、丁苯酞灌胃。而假手术组、模型组则给予生理盐水灌胃。各组分别于术后第3、7、14天处死,取梗阻侧肾组织做免疫组化染色以及western blot。结果:(1)Nrf-2在正常肾组织中仅散在表达于肾小管上皮细胞中,模型组术后第3、7、14天小鼠肾组织中Nrf-2表达均增加,治疗组小鼠肾组织Nrf-2随着输尿管梗阻时间的延长,Nrf-2表达逐渐增强,至14 d时表达达到顶峰,呈时间依赖性。(2)与模型组相比,丁苯酞治疗组Nrf-2、γ-GCS明显升高、Ⅰ型胶原蛋白表达明显减少(P<0.05),Nrf-2、γ-GCS在第7、14天表达均强于贝那普利组(P<0.05)。相关性分析显示:Nrf-2与γ-GCS呈正相关(r=0.930);与Ⅰ型胶原蛋白呈负相关(r=-0.859)。结论:丁苯酞可能通过激活Nrf-2通路,上调γ-GCS的表达,缓解氧化应激对肾间质的损伤,延缓肾间质纤维化进展。更多还原

【Abstract】 Objective To study on the possible mechanism of butylphthalide delaying renal fibrosis of mice with obstructive nephropathy. Methods Totally 72 male CD-1 mice of clean grade were selected and randomly assigned into 4 groups:sham operation group(Sham),model group(UUO),control group(ACEI)and treatment group(NBP). The mice in the control group(ACEI) and the treatment group(NBP) were given benazepril and butylphthalide by gavage,and the mice in sham operation group(Sham) and model group(UUO) were given normal saline by gavage. Six mice were sacrificed at the third,7th,14 th day,respectively.The obstructive renal tissue was selected for immunohistochemical staining and western blot. Results(1)With the longer time of ureteral obstruction,the expression of Nrf-2 was gradually strengthened in time-dependent manner;(2)Compared with the model group,the levels of Nrf-2 and γ-GCS in butylphthalide group were significantly increased,and the expression of type Ⅰ collagen was decreased significantly(P < 0.05). The expression of Nrf-2and γ-GCS in each time points was stronger than that in the benazepril group(P < 0.05). Correlation analysis showed that:there was a positive correlation between Nrf-2 and γ-GCS(r = 0.930) and a negative correlation between Nrf-2 and the expression level of type Ⅰ collagen(r =-0.859). Conclusion Butylphthalide can relieve renal interstitial injury caused by oxidative stress and delay the progress of renal interstitial fibrosis by activation of Nrf-2 pathway and up-regulated expression of γ-GCS.更多还原