【目的】 观察积雪草苷调节Hippo-yes相关蛋白（YAP）/具有PDZ结合基序的转录共激活因子（TAZ）信号通路对糖尿病肾 病（DN）大鼠肾纤维化的影响。【方法】 采用高糖高脂饲料喂养结合腹腔注射链脲佐菌素（STZ）法构建DN大鼠模型。将造模成 功的大鼠随机分为模型组，积雪草苷低、高剂量组及积雪草苷高剂量+XMU-MP-1（Hippo-YAP/TAZ通路激活剂）组，另设正 常组。分组干预后，检测大鼠血尿素氮（BUN）、血清肌酐（SCr）、空腹血糖（FBG）以及 24 h尿蛋白，苏木精-伊红（HE）染色 法观察肾组织病理变化，Masson染色法观察肾纤维化，Western Blot法检测肾组织YAP、TAZ的蛋白表达。【结果】 与正常组 比较，模型组肾组织肌束紊乱，囊腔轮廓大而不规则，肾小管体积变大且基底膜较厚，并有炎症细胞浸润，肾小球、肾小 管以及血管壁间质丝状胶原沉淀明显，FBG、BUN、SCr、24 h尿蛋白水平及肾组织YAP、TAZ蛋白表达水平升高（P＜0.05）； 与模型组比较，积雪草苷低、高剂量组肾组织损伤和肾纤维化得到明显改善，FBG、BUN、SCr、24 h尿蛋白水平及肾组织 YAP、TAZ蛋白表达水平降低（P＜0.05）；与积雪草苷高剂量组比较，积雪草苷高剂量+XMU-MP-1组上述各指标水平均被逆 转。【结论】 积雪草苷可能通过抑制Hippo-YAP/TAZ通路减轻DN大鼠肾纤维化，从而改善肾损伤。

Objective To observe the effects of asiaticoside on renal fibrosis in diabetic nephropathy （DN） rats by regulating the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. Methods A DN rat model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. The successfully modeled rats were randomly divided into model group，low- and high-dose asiaticoside groups，and high-dose asiaticoside + XMU-MP-1（Hippo-YAP/ TAZ pathway activator） group，with a normal group set as control. After group intervention，blood urea nitrogen （BUN）， serum creatinine（SCr）， fasting blood glucose（FBG）， and 24-hour urinary protein levels were measured. Hematoxylin-eosin（HE） staining was used to observe renal histopathological changes，Masson staining was used to assess renal fibrosis，and Western Blot was used to detect the protein expressions of YAP and TAZ in renal tissue. Results Compared with the normal group，the model group showed disordered renal tissue structure， enlarged and irregular cystic cavities，enlarged renal tubules with thickened basement membranes，inflammatory cell infiltration， and significant collagen deposition in the glomeruli， renal tubules， and vascular walls. The levels of FBG，BUN，SCr，24-hour urinary protein，and the protein expressions of YAP and TAZ in renal tissue were significantly increased （P＜0.05）. Compared with the model group， the low- and high-dose asiaticoside groups showed significant improvement in renal tissue damage and fibrosis，with reduced levels of FBG，BUN， SCr，24-hour urinary protein，and decreased protein expressions of YAP and TAZ in renal tissue （P＜0.05）. Compared with the high-dose asiaticoside group， the high-dose asiaticoside + XMU-MP-1 group showed a reversal in all the above indicators. Conclusion Asiaticoside may alleviate renal fibrosis and improve renal injury in DN rats by inhibiting the Hippo-YAP/TAZ pathway.

R285.5

山东省医药卫生科技发展计划项目（编号：202203051068）