蓝莓对大鼠肝纤维化PI3K-Akt信号通路影响

目的 观察磷脂酰肌醇-3激酶/蛋白激酶（PI3K/Akt）信号通路在猪血清所致的免疫性大鼠肝组织纤维化中作用及蓝莓影响。方法 60只健康雄性SD大鼠随机分为对照组、模型组、蓝莓原浆低、中、高剂量组（每天灌胃给予0.25、0.50、1.00 mL/100 g）及复方鳖甲软肝片组（每天灌胃0.054 g/100 g），每组10只，除对照组外，其余各组均采用每周二、五腹腔注射猪血清复制大鼠肝纤维化模型，共12周；测定大鼠肝脏指数及血清丙氨酸转氨酶（ALT）、谷草转氨酶（AST），观察肝组织病理学改变，采用免疫组织化学、Western blot法检测肝组织Akt1、磷酸化Akt1（p-Akt1）表达。结果 与对照组比较，模型组大鼠肝脏指数（0.58±0.02）明显升高（P<0.01），肝纤维化明显；与模型组比较，蓝莓高剂量组大鼠肝指数（0.37±0.06）明显降低（P<0.01），肝纤维化程度明显减轻；与对照组比较，模型组大鼠肝组织中Akt1、p-Akt1 蛋白表达量[分别为（0.99±0.09）、（0.81±0.06）]明显增加（P<0.01）；与模型组比较，蓝莓高、中剂量组大鼠肝组织中Akt1、p-Akt1 蛋白表达量[分别为（0.39±0.13）、（0.42±0.15）与（0.44±0.06）、（0.43±0.12）]明显下调（P<0.01）。结论 蓝莓对大鼠免疫性肝纤维化发生发展过程具有干预作用，其机制可能与PI3K/Akt信号通路激活有关。

Effect of blueberry on PI3K/Akt signaling pathway in rats with hepatic fibrosis

Objective To observe the change in phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway in rats with hepatic fibrosis induced by porcine serum immunization and to explore the effect of blueberry on the change of the signaling pathway.Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into a normal control group,a hepatic fibrosis model group,three blueberry treatment groups (at dosages of 0.25,0.50,and 1.00 ml juice/100 g body weight by gavage daily),and a Compound Biejiaruangan Troche (CBT,an traditional Chinese patent medicine made mainly of Carapax Trionycis,Panax notoginseng,Radix Paeoniae Rubra,Ophiocordyceps sinensis,and Forsythia suspense,at dose of 0.054 g/100 g body weight by gavage daily).All the rats,except for those of the normal control group,were injected intraperitoneally with porcine serum twice a week(on second and fifth weekday)for 12 weeks to establish hepatic fibrosis model;the rats of blueberry and CBT group were administered,respectively,with blueberry juice and CBT simultaneously.All the rats were sacrificed by the end of 12-week treatment.Liver index,serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.Pathological changes in the hepatic tissue were observed with hematoxylin-eosin (HE) staining.The expression of protein kinase B (Akt1) and phosphorylated Akt1 (p-Akt1) were detected with immunohistochemistry and Western blot.Results Compared with in the normal control group,the liver index (0.58±0.02) increased significantly (P<0.01) and liver fibrosis was obvious in the liver fibrosis model;while,the liver index (0.37±0.06) was significantly lower (P<0.01)and liver fibrosis was alleviated in the blueberry treatment groups compared to those in the liver fibrosis model group.Compared with hepatic fibrosis model group,the expression of Akt1 (0.99±0.09) and p-Akt1 (0.81±0.06) were significantly increased in the liver fibrosis model group (both P<0.01) compared to those in the control group;whereas the expressions of Akt1 (0.39±0.13 and 0.42±0.15) and p-Akt1 (0.44±0.06 and 0.43±0.12) were significantly decreased in the moderate and high dose blueberry treatment groups compared to those in the liver fibrosis model group (both P<0.01).Conclusion Blueberry can impact the development of immune hepatic fibrosis in rats and the effect may be related to the activation of PI3K/Akt signaling pathway.