小檗碱对大鼠自体原位肝脏移植肾脏损伤的影响

Berberine protects against kidney ischemia/reperfusion injury caused by autologous orthotopic liver transplantation in rats via activate Akt pathway

目的:探讨小檗碱对大鼠自体原位肝脏移植引起的肾脏损伤的保护作用及Akt信号通路在该过程中的作用。方法:健康雄性SD大鼠24只,随机分为假手术组(S组)、自体原位肝脏移植组(AT组)、自体原位肝脏移植模型+小檗碱处理组(BBR组),每组8只。S组接受麻醉后仅开腹,游离肝脏周围血管及韧带,关腹。AT组采用自体肝脏移植模型。BBR组大鼠术前连续灌胃7 d[200 mg/(kg·d)],手术操作同AT组。分别于再灌注8 h经下腔静脉取血,留取肾脏组织,比较各组之间的肾脏功能(BUN、Cr),肾脏组织形态学变化,超氧化物歧化酶(SOD)、丙二醛(MDA),p-Akt蛋白表达水平和凋亡细胞计数结果。结果:AT和BBR组BUN、Cr、MDA水平,p-Akt蛋白表达水平和凋亡细胞计数均高于S组。AT组BUN、Cr、MDA水平和凋亡细胞计数均高于BBR组,p-Akt蛋白表达水平低于BBR组。AT和BBR组肾脏组织SOD水平均低于S组,AT组较BBR组降低更明显。S组肾脏组织形态结构未见异常,AT组和BBR组损伤明显,BBR组损伤较AT组减轻。结论:小檗碱可能通过激活Akt信号通路抑制大鼠自体原位肝脏移植引起的肾小管上皮细胞凋亡。

Objective：To explore the protective effects of berberine（BBR）against kidney damage caused by autologous orthotopic liver transplantation（OLAT）. Methods：Sprague-Dawley rats were randomly divided into three groups（n =8）：（1）sham group（S group）;（2）autotransplantation（AT group）;（3）autotransplantation plus BBR group（BBR group）. In S groups,rats were anesthetized and simply freed the blood vessels and ligaments. In AT groups,rats underwent autologous orthotopic liver transplantation. In BBR groups, berberine was administered intragastricly 200 mg/（kg·d） for 7 days before autotransplantation. At eight hours after surgery, the rats were killed and the kidneys were harvested for determination of BUN, Cr,histologic injury,superoxide dismutase（SOD）,malondialdehyde（MDA）,the protein expression levels of p-Akt and the count of cell apoptosis. Results： MDA,BUN, Cr, protein expression levels of p-Akt and the count of cell apoptosis were significantly higher in the AT and BBR groups than in the S group. These indicators including MDA, BUN,Cr and the count of cell apoptosis was significantly higher in the AT group than in the BBR group. In the BBR group, protein expression levels of p-Akt were higher than those in the AT group.The levels of SOD were significantly lower in the AT group and BBR group than in the S group.The levels of SOD in the BBR group were greatly higher than in the AT group. Light microscopy demonstrated that histological tissue damage greatly reduced in the BBR group as compared to the AT group,while no injury was discovered in the s group. Conclusion： Berberine can protect against kidney ischemical/reperfusion injury during autotransplantation in rats, which might be ascribed to activate Akt pathway.