白芍总苷对系统性红斑狼疮模型大鼠Trap1基因多态性与维生素D代谢的影响

Effect of Total Glucosides of Paeonia on Trap1 Polymorphism and Vitamin D Metabolism in Model Rats with Systemic Lupus Erythematosus

目的探讨白芍总苷对系统性红斑狼疮(SLE)模型大鼠肿瘤坏死因子受体相关蛋白1(TRAP1)基因多态性与维生素D代谢的影响。方法选取雄性SD大鼠50只,将其随机分为空白组(等体积生理盐水)、模型组(等体积生理盐水)及白芍总苷低、中、高剂量组(0.5,1,5g/mL),各10只。腹腔注射降植烷,每只0.5mL,每周1次,连续3周,以复制SLE大鼠模型,建模成功后,各组大鼠分别灌胃给予相应药物及生理盐水。检测大鼠尿蛋白水平;采用苏木素-伊红(HE)染色,显微镜下观察大鼠肾脏组织病理形态;电化学发光法检测大鼠血清25(OH)D、1,25(OH)_(2)D_(3)水平;提取大鼠Trap1基因,记录各基因型的分布情况;分别采用反转录聚合酶链式反应法及Western blot法检测大鼠核因子κB(NF-κB)mRNA及其蛋白表达水平。结果与模型组比较,白芍总苷中、高剂量组大鼠尿蛋白阳性例数较少,且随着剂量的增加而减少(P<0.05);白芍总苷各剂量组肾纤维化减轻、炎症减少,25(OH)D、1,25(OH)_(2)D_(3)水平均明显升高,NF-κB mRNA及其蛋白表达水平均明显降低(P<0.05)。Trap1不同基因型(AA,AB,BB型)在各组大鼠中的分布情况基本一致。结论白芍总苷可改善SLE模型大鼠维生素D代谢不足,而对Trap1基因多态性并无明显影响,其可能通过调控NF-κB信号通路实现。

Objective To investigate the effect of total glucosides of paeonia(TGP)on tumor necrosis factor receptor-associated protein-1(TRAP1)gene polymorphism and vitamin D metabolism in model rats with systemic lupus erythematosus(SLE).Methods A total of 50 male SD rats were selected and randomly divided into the blank group(equal volume of normal saline),model group(equal volume of normal saline)and TGP low-,medium-and high-dose groups(0.5,1,5g/mL),with 10 rats in each group.The rats were intraperitoneally injected with decalin to establish SLE rat model,0.5mL each for each rat,once a week for three consecutive weeks.After successful modeling,the rats in each group were given intragastric administration of corresponding drugs or normal saline.The level of urinary protein was detected.Hematoxylin-eosin(HE)staining was used to observe the histopathological morphology of the kidney under the microscope.The levels of serum 25(OH)D and 1,25(OH)_(2)D_(3) were measured by the electrochemiluminescence method.The Trap1 gene of rats was extracted and the distribution of each genotype was recorded.Reverse transcriptase polymerase chain reaction(PCR)and Western blot were used to detect the expression levels of nuclear factor-κB(NF-κB)mRNA and protein.Results Compared with those in the model group,the number of positive cases of urine protein in the TGP medium-and high-dose groups with different doses were fewer,which decreased with the increase of dose(P<0.05),the renal fibrosis and inflammation in the TGP low-,medium-and high-dose group were alleviated.Compared with those in the model group,the levels of serum 25(OH)D and 1,25(OH)_(2)D_(3) in the TGP low-,medium-and high-dose group were significantly higher(P<0.05),the expression levels of NF-κB mRNA and protein in the TGP low-,medium-and high-dose groups were significantly lower(P<0.05).The distribution of different genotypes(AA,AB,BB)types in each group was similar.Conclusion TGP can improve vitamin D metabolism in SLE model rats by regulating NF-κB signaling pathway,but has no significant effect on Trap1 gene polymorphism.