化瘀通络中药鳖甲煎丸对肝纤维化大鼠PDGF及Ras信号转导通路的影响  

Influence of Biejiajian pill on PDGF and Ras signaling pathways in hepatic fibrosis in rats

作　　者：张艺凡[1] 王飞[2] 李风华[3] 孙玉凤[3] 张岩[4] 郭沛然[3] 何莉莉[3] 朱雅娜[3] 

机构地区：[1]河北省石家庄市第一医院中西医结合科,河北省石家庄市050011 [2]河北省沧州市中西医结合医院消化内科,河北省沧州市061001 [3]河北医科大学第二医院消化内科,河北省石家庄市050000 [4]河北省石家庄市第三医院保健科,河北省石家庄市050011

出　　处：《世界华人消化杂志》2014年第27期4060-4067,共8页World Chinese Journal of Digestology

基　　金：河北省自然科学基金资助项目;No.C2009001143~~

摘　　要：目的:探讨化瘀通络中药对肝纤维化(hepatic fibrosis,HF)的可能作用机制.方法:四氯化碳(carbon tetrachloride,CCl4)皮下注射的方法建立HF大鼠模型,将其随机分为对照组、模型组、中药低、中、高剂量组.造模开始时中药低、中、高剂量组大鼠分别给予化瘀通络中药鳖甲煎丸0.55、1.10、2.20 g/(kg?d)灌胃,正常对照组及模型组给予等体积的生理盐水灌胃,共6 wk.成模后继续灌胃5 wk.于第11周末,观察各组大鼠肝脏病理形态学变化;RT-PCR法检测肝组织中血小板衍生生长因子(platelet derivative growth factor,PDGF)、Ras基因表达水平;免疫组织化学方法检测肝组织细胞外信号调节激酶(extracellular signal regulated kinase,ERK1)蛋白表达.结果:与对照组相比,模型组大鼠肝组织PDGF、Ras、ERK1蛋白表达明显升高(0.190±0.001 vs 0.710±0.018,0.120±0.000 vs 0.420±0.006,0.120±0.000 vs 0.440±0.017,P<0.05);与模型组相比,化瘀通络中药鳖甲煎丸能够显著减轻HF大鼠肝脏组织病理损害,下调PDGF、Ras、ERK1蛋白的表达,其中以高剂量组效果最为显著.结论:鳖甲煎丸可明显减轻HF的病理损害,这一作用的实现可能是通过PDGF介导的Ras/ERK信号转导通路实现的.AIM： To explore the anti-fibrotic mechanism ofBiejiajian pill, a traditional Chinese medicine for activating blood circulation and eliminating sta- sis, in rats with hepatic fibrosis.METHODS： Hepatic fibrosis was induced in rats by subcutaneous injection of CCl4. SD rats were randomly divided into five groups： a control group, a model group, low-, medium- and high-dose Biejiajian pill treatment groups. The three treatment groups were given Biejia-jian pill 0.55, 1.10, and 2.20 g/（kgod）, respec- tively, while the normal control group and model group were treated with equal volume of normal saline by gavage. At the 11th week, hepatic pathological changes were observed. The immunohistochemical technique was ap- plied to analyze the expression of extracellular signal regulated kinase 1 （ERK1） in hepatic tissue. RT-PCR was applied to analyze the ex- pression of platelet derivative growth factor （PDGF） and Ras mRNAs in hepatic tissue.RESULTS： Compared with the control group, the expression levels of ERK1 protein and PDGF and Ras mRNAs increased significantly in the model group （0.19 ± 0.001 vs 0.71 ± 0.018, 0.12 ± 0.000 vs 0.42 ＋ 0.006, 0.12 ±0.000 vs 0.44 ± 0.017, P 〈 0.05）. Compared with the model group, Biejiajian pill significantly improved hepatic pathological changes and decreased the expression of ERK1 protein and PDGF and Ras mRNAs, and the efficacy of high-dose Biejiajian pill was the best.CONCLUSION： Biejiajian pill can improve he- patic pathological changes in rats with hepatic fibrosis possibly via mechanisms associated with activating the Ras/ERK signaling path- way.

关 键 词：肝纤维化 化瘀通络中药 鳖甲煎丸 血小板衍生生长因子 RAS 细胞外信号调节激酶 

分 类 号：R285.5[医药卫生—中药学]