目的 探讨蛋白激酶B（Akt）/FoxO3a通路在白藜芦醇抑制肾脏纤维化中的作用。方法 将55只SD大鼠随机分为假手术组（10只）和造模组（45只），采用单侧输尿管梗阻法构建大鼠肾间质纤维化模型，45只造模SD大鼠术后随机分为模型组和白藜芦醇（20、40 mg/kg）干预组，每组15只。干预组大鼠于术后ig白藜芦醇20、40 mg/kg，1次/d，持续2周。模型组大鼠ig等量生理盐水。HE、Masson染色观察肾组织病理变化，免疫组化检测α-SMA阳性细胞，Western blot检测Akt、p-Akt、FoxO3a、p-FoxO3a蛋白。结果 假手术组、模型组、白藜芦醇20 mg/kg干预组和白藜芦醇40 mg/kg干预组肾小管损伤病理评分分别为（0.36±0.05）、（4.07±0.53）、（3.92±0.48）和（3.21±0.35），其中白藜芦醇20 mg/kg干预组与模型组间无显著性差异，假手术组评分显著低于白藜芦醇干预组（P<0.05），白藜芦醇40 mg/kg干预组又显著低于造模对照组（P<0.05）。假手术组、模型组和白藜芦醇40 mg/kg干预组α-SMA阳性细胞比例分别为（3.84±0.62）%、（52.36±14.27）%和（26.15±4.63）%，3组间具有显著性差异（P<0.01）。FoxO3a和Akt蛋白表达三组间无显著性差异，p-Akt和pFoxO3a蛋白表达在模型组SD大鼠显著减低，但白藜芦醇40 mg/kg干预组p-Akt和p-FoxO3a蛋白表达高于模型组，低于假手术组。结论 白藜芦醇可以减低p-Akt和p-FoxO3a蛋白表达，发挥抗肾间质纤维化作用。

Objective To investigate the role of protein kinase B (Akt)/FoxO3a pathway in the inhibition of renal fibrosis by resveratrol. Methods 55 SD rats were devided into sham-operated group (10 rats) and model group (45 rats). The rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction. 45 SD rats were randomly divided into model group and resveratrol (20, 40 mg/kg) intervention group, and each group had 15 rats. The rats in the intervention group were ig 20, 40 mg/kg resveratrol, once daily for 2 weeks. The rats in model group received the same amount of normal saline. HE and Masson staining was used to observe renal pathological change. α-SMA positive cells were detected by immunohistochemical staining. Akt, p-Akt, FoxO3a, and p-FoxO3a were detected by Western blot analysis. Results The pathological scores of renal tubular injury in shamoperated group, model group, resveratrol 20 mg/kg intervention group, and resveratrol 40 mg/kg intervention group were (0.36 ±0.05), (4.07 ±0.53), (3.92 ±0.48), and (3.21 ±0.35), respectively. There was no significant difference between resveratrol 20 mg/kg intervention group and model control group. The scores in sham-operated group was significantly lower than that in the resveratrol intervention group (P<0.05), and resveratrol (40 mg/kg) intervention group was lower than that in model control group (P<0.05). The percentage of alpha-SMA positive cells in sham-operated group, model group, and resveratrol 40 mg/kg intervention group was (3.84±0.62)%, (52.36±14.27)%, and (26.15±4.63)%, respectively. There was significant difference among the three groups (P<0.01). There was no significant difference of FoxO3a and Akt protein expression among the three groups. The p-Akt and p-FoxO3a protein expression in model group SD rats was decreased significantly. However, the expression of p-Akt and p-FoxO3a protein in resveratrol 40 mg/kg intervention group was higher than that in model control group, and lower than that in sham-operated group. Conclusion Resveratrol can reduce the expression of p-Akt and p-FoxO3a protein and play an Anti-renal interstitial fibrosis role.

海南省自然科学基金（20158333）