丹酚酸B对慢性酒精性肝损伤大鼠肝脏的保护作用

Protective effects of Salvianolic acid B on alcoholic liver injury in rats

目的探讨丹酚酸B通过调控丝氨酸/苏氨酸蛋白激酶组成的异源三聚体依赖的蛋白激酶α1(AMPKα1)激活沉默信息调节因子2相关酶I(SIRT1)减轻酒精性肝损伤(ALD)的作用机制。方法用酒精液体饲料喂养建立ALD大鼠模型;另选大鼠普通饲料喂养作为空白组和对照组,将造模成功大鼠随机分为3组:模型组、低、高剂量实验组;每组均为8只。对照组、低、高剂量实验组灌胃给予丹酚酸B溶液30,15,30 mg·kg-1;空白组和模型组灌胃给予等量的0.9%NaCl,连续给药8周。用试剂盒检测丙氨酸氨基转移酶(ALT)水平。用蛋白免疫印迹法(Western Blot)检测大鼠肝脏组织SIRT1、AMPKα1及p-AMPKα1的蛋白表达情况。结果空白组、对照组、模型组、低、高剂量实验组的血清ALT水平分别为(24.37±2.08),(23.09±1.02),(59.97±3.68),(43.39±2.91)和(39.08±2.17)U·L-1;SIRT1蛋白表达相对水平分别为0.60±0.02,0.75±0.03,0.13±0.02,0.20±0.01,0.27±0.01;p-AMPKα1蛋白表达相对水平分别为1.01±0.01,1.52±0.10,0.45±0.02,0.62±0.04,0.71±0.05。模型组与空白组比较,低、高剂量组与模型组比较,上述指标的差异均有统计学意义(均P<0.01)。结论丹酚酸B通过调控AMPKα1磷酸化水平激活SIRT1蛋白表达,进而发挥其抗慢性酒精性肝病的保护作用。

Objective To explore whether salvianolic acid B-mediated up-regulation of silent information regulator 2-related enzymes1(SIRT1) is associated with adenosine monophosphate-activated protein kinase α1(AMPKα1) regulation to alleviate the chronic alcoholic liver disease(ALD) of rats. Methods The rats were fed with liquid alcoholic diet to establish ALD rat model. The other rats were fed with normal feeding as blank group and control group. After making the model successfully, rats were randomly divided into 3 groups: Model group, test-L group and test-H group;each group had 8 rats. Control group, test-L group and test-H group were given of 30,15,30 mg·kg-1 salvianolic acid B solution;blank group and model group were given the same amount of saline. Gavage administration was performed, qd for 6 weeks. The levels of alanine aminotransferase(ALT) were detected by kit. The expressions of SIRT1, AMPKα1 and p-AMPKα1 in the liver were detected by Western blotting. Results The serum ALT contents in blank group, control group, model group, test-L group and test-H group were(24. 37 ± 2. 08),(23. 09 ± 1. 02),(59. 97 ± 3. 68),(43. 39 ± 2. 91) and(39. 08 ± 2. 17) U · L-1;the levels of SIRT1 were0. 60 ± 0. 02,0. 75 ± 0. 03,0. 13 ± 0. 02,0. 20 ± 0. 01,0. 27 ± 0. 01;the levels of p AMPKα1 were 1. 01 ± 0. 01,1. 52 ± 0. 10,0. 45 ± 0. 02,0. 62 ± 0. 04,0. 71 ± 0. 05. There were significant differences in the above factors between model group and blank group(all P < 0. 01). Comparing between test-L group and test-H group with model group,the differences were also significant(all P < 0. 01). Conclusion Salvianolic acid B activates the expression of SIRT1 through regulating the phosphorylation levels of AMPKα1,which make great contributions to its protection against ALD.