汉丹肝乐对大鼠肝纤维化PI3K/Akt信号通路的影响及意义  

Handan Ganle inhibits PI3K/Akt signaling pathway in liver fibrosis in rats

作　　者：胡晓霞[1] 王艳[1] 王晋星一[1] 

机构地区：[1]贵阳医学院生理学教研室,贵州省贵阳市550004

出　　处：《世界华人消化杂志》2014年第14期1915-1920,共6页World Chinese Journal of Digestology

摘　　要：目的:观察磷脂酰肌醇-3激酶/蛋白激酶(phosphatidylinositol-3 kinase/Akt,PI3K/Akt)信号通路在CCl4诱导的肝纤维化大鼠肝组织中的变化并探讨中药汉丹肝乐对他的影响.方法:选取SD大鼠30只,随机分为正常对照组、肝纤维化8 wk组及汉丹肝乐治疗组,每组各10只.肝纤维化组及汉丹肝乐治疗组大鼠按0.3 mL/100 g体质量的剂量皮下注射40%CCl4花生油溶液,每隔3 d注射1次,造模时间为8wk;对照组大鼠皮下注射等量花生油溶液.造模结束后汉丹肝乐治疗组大鼠给予1.0 g/kg的汉丹肝乐灌胃治疗,1次/d,治疗时间为8 wk.HE染色观察肝组织病理学改变;采用免疫组织化学技术及Western blot检测肝组织中PI3K/Akt信号通路中关键分子Akt1、磷酸化Akt1的表达变化,同时应用TUNEL法检测肝星状细胞(hepatic stellate cells,HSC)凋亡情况.结果:与正常对照组比较,肝纤维化8 wk组大鼠肝组织中Akt1(2.73±0.52 vs 9.60±2.28,P<0.01)、磷酸化Akt1(0.92±0.40 vs 6.51±1.39,P<0.01)的表达均显著增加,差异具有显著性;经汉丹肝乐治疗后,肝组织中Akt1(9.60±2.28 vs 5.36±1.59,P<0.01)、磷酸化Akt1(6.51±1.39 vs 2.08±0.85,P<0.01)的表达均显著下降;同时,TUNEL法检测发现汉丹肝乐组大鼠肝组织中HSC凋亡率显著高于肝纤维化8 wk组(1.07±0.32 vs 4.24±0.86,P<0.01).结论:PI3K/Akt信号通路在肝纤维化的发生发展过程中发挥重要作用,而汉丹肝乐可通过抑制该信号通路,促进HSC的凋亡来发挥抗肝纤维化的作用.AIM： To observe the change of the PI3K/Akt signaling pathway in CCl4 induced liver fibrosis and to explore the effect of Handan Ganle on this signaling pathway in hepatic fibrosis in rats. METHODS： Thirty SD rats were randomly divided into a normal control group, a liver fibrosis group and a Handan Ganle treated group. The rats of the liver fibrosis group and Handan Ganle treated group were treated by hypodermic injection of 40% CCl4 at 0.3 mL/100 g body weight to induce hepatic fibrosis. Then, the rats in the Handan Ganle group were treated with 1.0 g/kg Handan Ganle once daily for 8 weeks. The expression of Akt1 and phospho-Akt1 was detected by immunohistochemistry and Western blot, and the apoptosis of HSCs was determined by TUNEL assay. RESULTS： Compared with the normal control group, the expression of Akt1（2.73 ± 0.52 vs9.60 ± 2.28, P 0.01） and phospho-Akt1（0.92 ± 0.40 vs 6.51 ± 1.39, P 0.01） in the liver fibrosis group was increased. Handan Ganle treatment decreased the levels of Akt1（9.60 ± 2.28 vs 5.36 ± 1.59, P 0.01） and phospho-Akt1（6.51 ± 1.39 vs 2.08 ± 0.85, P 0.01） but increased the apoptosis of HSCs（1.07 ± 0.32 vs 4.24 ± 0.86, P 0.01）. CONCLUSION： The PI3K/Akt signaling pathway may play an important role in CCl4 induced liver fibrosis. Handan Ganle can suppress this signaling pathway and increase the apoptosis of HSCs, which might be related with its antihepatic fibrosis activity.

关 键 词：肝纤维化 磷脂酰肌醇-3激酶 蛋白激酶 肝星状细胞 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]