Objective To observe the effect of Guizhi Fuling capsule on the expressions of α-smooth muscle actin (α-SMA), collagen Ⅳ and transforming growth factor-betal (TGF-pl) in rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO). Methods TIF model was established via UUO in SD rats. Seventy-two SD rats were randomly divided into three groups, sham-operated group (n=24), model group (n=24) and treatment group (n=24). Guizhi Fuling capsule of 250 mg/(kg·d) and normal saline were administered to rats in treatment group by nasal feeding twice a day, and an equal volume of normal saline at same time were administered to rats in model group and sham-operated group. Eight rats in each group were executed on 7, 14 and 21 days after nasal feeding, respectively. Renal histopathological changes such as renal tubular injury, inflammatory cell infiltration in tubulointerstitium and interstitial fibrosis were observed under light microscopy. The expressions of α-SMA, collagen IV and TGF-β1 in tubulointerstitium were observed and evaluated by immunohistochemistry. Results After a TIF model was established, progressive renal tubulointerstitial injury and fibrosis in obstructed kidney were seen. Compared with the model group, the degree of tubulointerstitial fibrosis in obstructed kidney of treatment group was significantly lower at same time point (P＜0.01). The expressions of α-SMA, collagen Ⅳ and TGF-β1 in obstructed kidney tobulointerstitium showed a gradual up-regulation trend over time. The severity of renal tubulointerstitial injury was positively correlated with the expressions of α-SMA, collagen IV and TGF-β1 (all P＜0.05). Conclusion Guizhi Fuling capsule may attenuate epithelial-to-mesenchymal transition (EMT) and decrease extracellular matrix deposition in interstitium by partial down-regulation of the expressions of α-SMA, collagen IV and TGF-β1, and may thus delay the development of TIF.%目的 观察桂枝茯苓胶囊对单侧输尿管梗阻(UUO)诱导大鼠小管间质纤维化(TIF)过程中α-平滑肌肌动蛋白(α-SMA)、Ⅳ型胶原(collagen Ⅳ)和转化因子-β1 (TGF-β1)表达的影响.方法 利用SD大鼠行UUO诱导建立TIF动物模型.72只SD大鼠随机分为假手术组(n=24)、模型组(n=24)和治疗组(n=24).治疗组给予桂枝茯苓胶囊+生理盐水灌胃,250 mg/(kg·d),每日2次；模型组和假手术组大鼠则在同一时间点以等体积生理盐水灌胃作对照.分别于实验第7、14、21天,3个时间点,三组各处死8只大鼠,检测肾小管损伤、间质炎症细胞浸润和纤维化等肾脏组织病理学变化,采用免疫组化观察和评价α-SMA、collagen Ⅳ和TGF-β1表达变化.结果 UUO模型建立后,梗阻肾小管间质损伤和纤维化呈进行性加重.在同一时间点,治疗组的肾小管间质纤维化程度比模型组大鼠明显减轻,差异有统计学意义(P＜0.01).梗阻肾小管间质α-SMA、collagen Ⅳ和TGF-β1的表达则呈逐渐上调趋势,且肾小管间质损害与α-SMA、collagenⅣ和TGF-β1表达量呈正相关(r=0.722～0.903,P均＜0.01).结论 桂枝茯苓胶囊可能通过下调α-SMA、collagenⅣ和TGF-β1表达,减轻肾小管上皮间充质转分化和细胞外基质在间质区域的过度沉积,从而达到延缓TIF进展的作用.
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