目的 探討蛋白激酶B（Akt）/FoxO3a通路在白藜蘆醇抑制腎臟纖維化中的作用。方法 將55只SD大鼠隨機(jī)分為假手術(shù)組（10只）和造模組（45只），采用單側(cè)輸尿管梗阻法構(gòu)建大鼠腎間質(zhì)纖維化模型，45只造模SD大鼠術(shù)后隨機(jī)分為模型組和白藜蘆醇（20、40 mg/kg）干預(yù)組，每組15只。干預(yù)組大鼠于術(shù)后ig白藜蘆醇20、40 mg/kg，1次/d，持續(xù)2周。模型組大鼠ig等量生理鹽水。HE、Masson染色觀察腎組織病理變化，免疫組化檢測(cè)α-SMA陽(yáng)性細(xì)胞，Western blot檢測(cè)Akt、p-Akt、FoxO3a、p-FoxO3a蛋白。結(jié)果 假手術(shù)組、模型組、白藜蘆醇20 mg/kg干預(yù)組和白藜蘆醇40 mg/kg干預(yù)組腎小管損傷病理評(píng)分分別為（0.36±0.05）、（4.07±0.53）、（3.92±0.48）和（3.21±0.35），其中白藜蘆醇20 mg/kg干預(yù)組與模型組間無(wú)顯著性差異，假手術(shù)組評(píng)分顯著低于白藜蘆醇干預(yù)組（P<0.05），白藜蘆醇40 mg/kg干預(yù)組又顯著低于造模對(duì)照組（P<0.05）。假手術(shù)組、模型組和白藜蘆醇40 mg/kg干預(yù)組α-SMA陽(yáng)性細(xì)胞比例分別為（3.84±0.62）%、（52.36±14.27）%和（26.15±4.63）%，3組間具有顯著性差異（P<0.01）。FoxO3a和Akt蛋白表達(dá)三組間無(wú)顯著性差異，p-Akt和pFoxO3a蛋白表達(dá)在模型組SD大鼠顯著減低，但白藜蘆醇40 mg/kg干預(yù)組p-Akt和p-FoxO3a蛋白表達(dá)高于模型組，低于假手術(shù)組。結(jié)論 白藜蘆醇可以減低p-Akt和p-FoxO3a蛋白表達(dá)，發(fā)揮抗腎間質(zhì)纖維化作用。

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.

海南省自然科學(xué)基金（20158333）