桂枝茯苓胶囊对肾小管间质纤维化大鼠骨调素和CD44表达的影响

The effect of Guizhifuling capsule on the expression of OPN/CD44 in tubuiointerstitial fibrosis rats

目的观察桂枝茯苓胶囊对小管间质纤维化（TIF）大鼠OPN和CD44表达的影响。方法利用SD大鼠行单侧输尿管梗阻（UUO）诱导建立TIF动物模型，72只SD大鼠随机分为假手术组（24只）、模型组（24只）和预防组（24只）。预防组接受桂枝茯苓胶囊管理（500mg·k^-1·d^-1），模型组、假手术组则以等体积生理盐水。3组分别于实验第7、14和21天3个时间点收获动物各8只。检测上述时间点各组动物肾脏小管损伤、间质炎症细胞浸润和纤维化等肾脏组织病理学变化特点。采用免疫组化观察和评价OPN／CD44在梗阻肾中表达以及桂枝茯苓胶囊对OPN／CD44表达的影响。结果梗阻肾在上述三个时间点小管间质损伤呈进行性加重。免疫组化结果显示OPN／CD44在TIF中呈高表达，且随着TIF的进展不断上升。桂枝茯苓胶囊可以降低OPN／CD44在TIF中的表达，与模型组比较差异有统计学意义（P〈0．01）。OPN／CD44在TIF中的表达同小管间质损伤程度呈正相关（r=0．78，0．77．P〈0．01）。结论桂枝茯苓胶囊部分通过下调OPN／CD44在梗阻肾中的表达，起到延缓小管间质纤维化进展的作用。

Objiectives To explore the effect of Guizhifuling capsule on the expression of osteopontin （OPN） and CD44 in tubulointerstitial fibrosis （TIF） rats. Methods 72 aged 3 months Sprague-Dawley male rats were random divided into three groups ： model group （ n = 24）, treatment group （ n = 24） and sham-operated group （ n = 24 ）. Tubulointerstitial fibrosis rat model was established via unilateral ureteral obstruction （UUO）. Rats in treatment group were administrated with Guizhifuling capsule （500mg · kg^-1 · d^-1 ）. Rats were killed on day 7, 14, 21 after experiment. The characteristic changes about interstitial inflammation, interstitial fibrosis and renal tubule damage were observed under light microscope at the same time. The expression of OPN and CD44 in TIF was detected by immunohistochemistry. Resuits Renal tubulointerstitium injury aggravated increased gradually at the three time points. Changes of histology in obstructed-kidney was characterized by interstitial inflammation, renal tubule damage and interstitial fibrosis. The expression of OPN/CD44 increased in TIF which induced by UUO, and gradually increased with development of tubulointerstitial injury. Guizhifuling capsule decreased the expression of OPN/CD44 in TIF, and gradually increased with development of tubulointerstitial injury. Guizhifuling capsule decreased the impression of OPN/CD44 in TIF, which was apparent different compared with model group （ P 〈 0. 01 ）. There was a positive relation between the expression Of OPN/CD44 in TIF and the degree of tubulointerstitial injury （ r = 0.78,0. 77, P 〈 0.01 ）. Conclusions Guizhifuling capsule slows the development of TIF by partly decreased the expression of OPN/CD44.