【摘要】 目的 基于轴抑制蛋白2/β-连环蛋白（Axin2/β-catenin）信号通路观察大承气汤对急性肾损伤大鼠的影响并初步探讨其作用机制。方法 将50只6～8周龄的C57BL/6J大鼠随机分为对照组、模型组、大承气汤低剂量组（3 g/kg）、大承气汤高剂量组（27 g/kg）、阳性对照组（5 mg/kg盐酸贝那普利）,每组10只。通过注射顺铂构建急性肾损伤模型。造模成功后,大承气汤低剂量组、大承气汤高剂量组、阳性对照组给予相应药物进行腹腔注射,对照组和模型组注射等体积生理盐水。酶联免疫吸附分析（ELISA）检测大鼠尿蛋白、尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）水平,血清中肌酐（SCr）、尿素氮（BUN）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平,以及肾组织中Fe²⁺、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平;苏木精-伊红（HE）染色观察大鼠肾组织形态变化;荧光定量PCR检测各组Axin2和β-catenin基因表达水平;蛋白质印迹法（Western blotting）检测大鼠肾组织中Axin2/β-catenin通路相关蛋白表达。结果 与对照组相比,模型组中大鼠尿蛋白量、尿NAG水平、SCr、BUN、IL-6、IL-1β、TNF-α、Fe²⁺、MDA水平、Axin2 mRNA表达和蛋白表达水平升高（P<0.05）,肾组织病理损伤加重,而GSH-Px、SOD水平、β-catenin mRNA表达和蛋白表达水平降低（P<0.05）。与模型组相比,大承气汤低剂量组、大承气汤高剂量组、阳性对照组中大鼠尿蛋白量、尿NAG水平、SCr、BUN、IL-6、IL-1β、TNF-α、Fe²⁺、MDA水平、Axin2 mRNA表达和蛋白表达水平降低（P<0.05）,肾组织病理损伤减轻,GSH-Px、SOD水平、β-catenin mRNA表达和蛋白表达水平升高（P<0.05）。结论 大承气汤能显著改善急性肾损伤大鼠肾功能,其机制可能是通过抑制Axin2的表达,增加β-catenin的积累,从而改善大鼠的肾损伤。更多还原

【Abstract】 Objective:To observe the effect of Dachengqi Decoction on rats with acute kidney injury based on Axin2/β-catenin signaling pathway and to preliminarily explore its mechanism. Methods:50 C57BL/6J rats aged 6～8 weeks were randomly divided into a control group,a model group,a low-dose Dachengqi Decoction group（3 g/kg）,a high-dose Dachengqi Decoction group（27 g/kg）,and a positive control group（5 mg/kg benazepril hydrochloride）,with 10 rats in each group. The acute kidney injury model was established by cisplatin injection. After successful modeling,the low-dose Dachengqi Decoction group,high-dose Dachengqi Decoction group,and positive control group were given corresponding drugs by intraperitoneal injection,while the control group and model group were injected with the same volume of normal saline. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of urinary protein and urinary N-acetyl-β-D-glucosaminidase（NAG）,serum creatinine（SCr）,blood urea nitrogen（BUN）,interleukin-6（IL-6）,interleukin-1β（IL-1β）and tumor necrosis factor-α（TNF-α）,as well as the levels of Fe²⁺,malondialdehyde（MDA）,superoxide dismutase（SOD）and glutathione peroxidase（GSH-Px）in renal tissues. Hematoxylin-eosin（HE）staining was used to observe the morphological changes of rat renal tissues. Fluorescent quantitative PCR was used to detect the mRNA expression levels of Axin2 and β-catenin in each group. Western blotting was used to detect the expression of Axin2/β-catenin pathway-related proteins in rat renal tissues. Results:Compared with the control group,the levels of urinary protein,urinary NAG,SCr,BUN,IL-6,IL-1β,TNF-α,Fe²⁺,MDA,and the mRNA and protein expression of Axin2 in the model group were significantly increased（P < 0.05）,the pathological damage of renal tissues was aggravated,while the levels of GSH-Px,SOD,and the mRNA and protein expression of β-catenin were significantly decreased（P < 0.05）. Compared with the model group,the levels of urinary protein,urinary NAG,SCr,BUN,IL-6,IL-1β,TNF-α,Fe²⁺,MDA,and the mRNA and protein expression of Axin2 in the low-dose Dachengqi Decoction group,high-dose Dachengqi Decoction group and positive control group were significantly decreased（P < 0.05）,the pathological damage of renal tissues was alleviated,and the levels of GSH-Px,SOD,and the mRNA and protein expression of β-catenin were significantly increased（P < 0.05）. Conclusion:Dachengqi Decoction can significantly improve renal function in rats with acute kidney injury,and its mechanism may be related to inhibiting the expression of Axin2 and increasing the accumulation of β-catenin,thereby alleviating renal injury in rats.更多还原