【目的】 探讨肾病Ⅰ号方对慢性肾衰竭大鼠的治疗作用及机制。【方法】 采用连续腺嘌呤灌胃法建立慢性肾衰竭大鼠模 型。建模成功后，将大鼠随机分为模型组，肾病Ⅰ号方低、高剂量组，每组10只。分组干预。干预结束后，采用苏木精- 伊红（HE）染色法观察肾组织病理变化，Masson染色法观察肾组织纤维化，免疫组织化学法检测肾组织胶原蛋白Ⅳ（Col-Ⅳ） 表达，Western Blot法检测肾组织黏着斑激酶（FAK）、Ras、丝裂原活化蛋白激酶（MAPK）的蛋白表达，采用体外实验验证肾 病Ⅰ号方对FAK-Ras-MAPK信号通路的作用。【结果】 与正常组比较，模型组肾间质纤维化面积增大，肾组织Col-Ⅳ及FAK、 Ras、MAPK蛋白表达水平升高，差异有统计学意义（P＜0.05）；与模型组比较，肾病Ⅰ号方低、高剂量组肾间质纤维化面积 缩小，肾组织Col-Ⅳ及FAK、Ras、MAPK蛋白表达水平降低，差异有统计学意义（P＜0.05），其中高剂量组效果更显著。体 外验证结果显示：与对照组比较，含药血清组细胞FAK、Ras、MAPK蛋白表达水平显著降低（P＜0.05）。【结论】 肾病Ⅰ号方 可有效改善肾衰竭大鼠肾纤维化，其机制可能与抑制FAK-Ras-MAPK信号通路有关。

Objective To investigate the therapeutic effects and mechanisms of Nephropathy FormulaⅠ（NF-Ⅰ） in rats with chronic renal failure （CRF）. Methods A CRF model was established using continuous adenine gavage. After successful modeling，the rats were randomly divided into normal group，model group，low-dose and highdose of NF- Ⅰ groups， with 10 rats in each group. The group-specific interventions were administered. Renal histopathological changes were observed via hematoxylin-eosin （HE） staining，renal fibrosis was evaluated using Masson staining，collagen Ⅳ（Col-Ⅳ） expression in renal tissues was detected by immunohistochemistry，and protein expression of focal adhesion kinase （FAK），Ras，and mitogen-activated protein kinase （MAPK） in renal tissues was analyzed via Western Blot. Additionally，in vitro experiments were performed to validate the effect of NF-Ⅰ on the FAK-Ras-MAPK signaling pathway. Results Compared with the normal group，the model group exhibited a significant increase in renal interstitial fibrosis area and elevated protein expression levels of Col-Ⅳ， FAK， Ras， and MAPK in renal tissues， and the differences were statistically significant （P＜0.05）. In comparison to the model group，both the NF-Ⅰ low-dose and high-dose groups showed significant reductions in renal interstitial fibrosis area and downregulation of Col-Ⅳ，FAK，Ras，and MAPK protein expression levels， and the differences were statistically significant （P＜0.05），while the effects in the high-dose group were superior. In vitro validation results demonstrated that，compared with the control group，the protein expression levles of cellular FAK，Ras and MAPK were decreased in drug-containing serum group （P＜0.05）. Conclusion NF-Ⅰ effectively ameliorates renal fibrosis in CRF rats， potentially through suppression of the FAK-Ras-MAPK signaling pathway.

R285.5

浙江省中医药防治重大疾病攻关计划项目（编号：2018ZY011）