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目的探讨抗增殖蛋白(PHB)在单侧输尿管结扎(UUO)致肾间质纤维化(RIF)大鼠肾脏组织中的表达及全反式维A酸(ATRA)对PHB表达的影响,为临床UUO发病机制研究及诊断和治疗提供依据。方法雄性6周龄Wistar大鼠72只随机分为假手术组、模型组和ATRA组,每组24只。术前1 d,ATRA组大鼠行ATRA灌胃[15 mg/(kg.d)],模型组和假手术组行等量9 g/L盐水灌胃。将模型组和ATRA组大鼠麻醉后在背侧切口行左侧输尿管结扎术,假手术组只探及肾包膜。造模后第7、14、21、28天各组分别处死6只大鼠,留取左侧肾脏常规石蜡包埋,制作切片行HE和Massion染色后观察肾脏病理变化,计算其RIF指数,采用免疫组织化学和实时荧光定量RT-PCR检测各组大鼠肾脏组织PHB蛋白和mRNA表达。结果1.与假手术组比较,模型组大鼠各时间点肾脏组织,RIF指数显著增高,梗阻时间越长,RIF指数越高;PHB蛋白和mRNA表达均显著降低(Pa<0.01),梗阻时间延长,PHB表达越低。2.模型组大鼠肾脏组织PHB蛋白的表达与RIF指数呈显著负相关(r=-0.825 P<0.01)。3.与模型组大鼠各时间点比较,ATRA组大鼠肾脏组织RIF指数显著下降(P<0.01),PHB蛋白和mRNA表达均显著增加(Pa<0.01)。结论在UUO大鼠肾脏组织中,PHB表达明显减少,可能参与了RIF的发生发展;ATRA可能通过增加PHB的表达而达到减缓RIF进展的作用。
Objective To investigate the expression of anti-proliferating protein (PHB) in renal tissue of rats with unilateral ureteral obstruction (UUO) induced by unilateral ureteral obstruction (UUO) and the effect of all-trans retinoic acid (ATRA) on the expression of PHB, UUO pathogenesis research and diagnosis and treatment provide the basis. Methods 72 male Wistar rats aged 6 weeks were randomly divided into sham operation group, model group and ATRA group, 24 rats in each group. The rats in ATRA group were treated with ATRA intragastrically [15 mg / (kg · d)] on the first day before operation. The rats in model group and sham operation group were treated with the same dosage of 9 g / L saline. The rats in model group and ATRA group were anesthetized and the left ureter was ligated in the dorsal incision. Only the renal capsule was examined in the sham operation group. Six rats were sacrificed on the 7th, 14th, 21st and 28th day after the model was established, respectively. The left kidney was collected and embedded in paraffin. The pathological changes of the kidney were observed by HE staining and Massion staining. The RIF index was calculated. Immunohistochemistry and real-time fluorescent quantitative RT-PCR were used to detect the expression of PHB protein and mRNA in kidney of each group. Compared with the sham-operation group, the RIF index of kidney tissue in model group at each time point was significantly increased, and the longer the obstruction time was, the higher the RIF index was; the expression of PHB protein and mRNA were significantly decreased (P <0.01) Prolonged, the lower the PHB expression. The expression of PHB protein in renal tissue of model rats was negatively correlated with RIF index (r = -0.825 P <0.01). Compared with the model rats at each time point, the RIF index of kidney in ATRA group decreased significantly (P <0.01), and the protein and mRNA expression of PHB increased significantly (Pa <0.01). Conclusion The expression of PHB in renal tissues of UUO rats decreased significantly, which may be involved in the development of RIF. ATRA may reduce the progression of RIF by increasing the expression of PHB.