水飞蓟素对肾小管间质纤维化大鼠核转录因子-κB和细胞间黏附分子-1表达的影响

Effects of Silymarin on Expressions of Nuclear Factor Kappa B and Intercellular Adhesion Molecule-1 in Renal Tissue of Rats with Tubulointerstitial Fibrosis

目的探讨水飞蓟素对大鼠肾间质纤维化的作用及对肾组织核转录因子-κB(NF-κB)和细胞间黏附分子-1(ICAM-1)表达的影响。方法72只SD大鼠随机分为假手术组、梗阻组、水飞蓟素治疗组(治疗组),每组24只。采用单侧输尿管结扎术建立输尿管梗阻动物模型。治疗组予水飞蓟素30 mg/(kg.d)灌胃,梗阻组和假手术组予9 g/L盐水灌胃。各组分别于实验7、14、21 d各处死大鼠8只,光镜下观察肾组织病理学改变。采用免疫组织化学法检测其肾组织NF-κB和ICAM-1的表达。结果梗阻组大鼠7、14、21 d的肾小管间质病理评分分别为1.168±0.108、1.776±0.064和2.301±0.157,治疗组大鼠7、14、21 d肾小管间质病理评分分别为1.043±0.114、1.677±0.083和2.084±0.201,治疗组肾小管间质评分较梗阻组明显减轻(Pa<0.05)。梗阻组大鼠7、14、21 d肾组织NF-κB和ICAM-1的表达分别为13.27±0.15、14.37±0.07、15.43±0.11和4.26±0.07、5.81±0.05、6.91±0.08,治疗组大鼠7、14、21 d肾组织NF-κB和ICAM-1的表达分别为8.35±0.18、9.39±0.10、10.77±0.10和3.24±0.05、4.25±0.12、5.30±0.11,治疗组肾组织NF-κB和ICAM-1的表达均较梗阻组明显减少(Pa<0.05)。结论水飞蓟素可能是通过下调NF-κB和ICAM-1表达而抑制纤维化的发生,从而起到对大鼠肾脏的保护作用。

Objective To investigate the effects of silymarin on expressions of nuclear factor kappa B （ NF - kB） and intercellular adhesion molecule - 1 （ ICAM - 1 ） in the kidneys of rats with unilateral ureteral obstruction （UUO） - induced renal fibrosis. Methods Seventy - two male Sprague - Dawley rats were randomly divided into 3 groups ： sham - operated group （ n = 24 ） , operated group （ n= 24 ） and silymarin treated group（n = 24 ）. Renal tubulointerstitial fibrosis model was established via UUO. Silymarin was given by gavage with 30 mg/ （kg ·d） in silymarin treated group, and the same volume normal saline was given by gavage in operated group and sham -operated group. In each group, 8 rats were killed at 7, 14 and 21 d after operation. Histological changes were observed in tubulointerstitial injury under mi- croscope. The expressions of NF -kB and ICAM - 1 in renal tissue were determined with immunohistochemical method. Results Tubulointerstitial injury scores in operated group at 7, 14 and 21 d were 1. 168 ± 0. 108, 1. 776 ± 0. 064 and 2. 301± 0. 157, respectively, and Tubulointerstitial injury scores in the treated group at 7, 14 and 21 d were 1. 043 ±0. 114, 1. 677 ±0. 083 and 2. 084 ± 0. 201, respectively. Tubulointerstitial injury scores in silymarin treated group were significantly lower than those in operated group （ Pa〈 0.05 ）. The expressions of NF - KB and ICAM - 1 in operated group at 7, 14 and 21 d were 13.27 ± 0.15, 14.37 ± 0.07, 15.43 ± 0.11 and 4.26 ±0.07, 5.81 ± 0.05, 6.91 ± 0.08, respectively. The expressions of NF - KB and ICAM - 1 in silymarin treated group at 7, 14 and 21 d were 8.35 ± 0.18, 9.39 ±0.10, 10.77±0. 10 and 3.24±0.05, 4.25 ± 0.12, 5.30± 0.11, respectively. The expressions of NF - KB and ICAM - 1 in silymarin treated group were also significantly down - regulated than those in operated group （ Pa 〈0. 05 ）. Conclusion Silymarin may inhibit renal fibrosis by down - regulated NF - KB and ICAM - 1 expressions, which may play a key role in protection against renal fibrosis.