汉丹肝乐对大鼠肝纤维化PI3KAkt信号通路的影响及意义.docVIP

汉丹肝乐对大鼠肝纤维化PI3K/Akt信号通路的影响及意义 胡晓霞, 王艳，王妮 （贵阳医学院 生理学教研室 贵州贵阳 550004） [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它的影响。 方法 选取SD大鼠30只, 随机分为正常对照组、肝纤维化8周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0.3ml/100g体重的剂量皮下注射40% CCl4花生油溶液，每隔3天注射1次，造模时间为8周；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，每日一次，治疗时间为8周。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周组大鼠肝组织中Akt1、磷酸化Akt1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、磷酸化Akt1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周组。 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。 [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 The effect of Han Dan Gan Le on PI3K/Akt signaling pathway in liver fibrosis HU Xiaoxia，WANGYan, WANG Ni （Department of physiology, Guiyang Medical College, Guiyang 550004, China）PI3K/Akt signaling pathway in CCl4 induced liver fibrosis and explore the effect of Han Dan Gan Le on this signaling pathway in hepatic fibrosis. Methods Thirty SD rats were randomly divided into normal control group，8 weeks liver fibrosis group and Han Dan Gan Le treated group. The _________________________________________________ 作者简介：胡晓霞（1978-），女，布依族，贵州长顺人，讲师，硕士，主要从事肝纤维化防治研究。 通讯作者：胡晓霞 贵州省贵阳医学院生理学教研室 550004 E-mail:hxx2000@163.com rats of liver fibrosis group and Han Dan Gan Le treated group were induced by hypodermic injection of 40% CCl4，the dosage of CCl4 is 0.3ml/100g body weight. Then, the rats in Han Dan Gan Le groups were treated with 1.0 g/kg Han Dan Gan Le by p.o everyday for 8 weeks. Detected the expression of Akt1, phospho-Akt1 by immunohistochemical techniques and western blot, the apoptosis of HSC was determined by TUNEL. Results Compared with the normal control group, the expression of Akt1, phospho-Akt1 in 8 weeks liver fibrosis group were increased. Through Han Dan Gan Le treatment, we found the levels of Akt1 and phospho-Akt1 were decreased, whil