[1]呙琳琳,戴立里,唐静.丹参素对PDGF-BB刺激下肝星状细胞的抑制作用[J].第三军医大学学报,2011,33(15):1610-1614.
 Guo Linlin,Dai Lili,Tang Jing.Salvianic acid A (Danshensu) inhibits proliferation and activation in rat hepatic stellate cells induced by platelet derived growth factor-BB[J].J Third Mil Med Univ,2011,33(15):1610-1614.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
33卷
期数:
2011年第15期
页码:
1610-1614
栏目:
论著
出版日期:
2011-08-15

文章信息/Info

Title:
Salvianic acid A (Danshensu) inhibits proliferation and activation in rat hepatic stellate cells induced by platelet derived growth factor-BB
作者:
呙琳琳戴立里唐静
重庆医科大学附属第二医院消化内科
Author(s):
Guo Linlin Dai Lili Tang Jing
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
关键词:
丹参素肝星状细胞血小板衍生生长因子-BB胶原
Keywords:
Danshensuhepatic stellate cellsplatelet derived growth factor-BBcollagen
分类号:
R285.5; R322.47; R329.28
文献标志码:
A
摘要:
目的     观察丹参素对PDGF-BB刺激下大鼠肝星状细胞活化增殖,Ⅰ、Ⅲ型胶原合成与分泌,ERK1/2和PI3K通道蛋白表达的影响,探讨丹参素抑制肝纤维化的分子机制。      方法       用不同浓度丹参素(0.250、0.125、0.062 mmol/L)、ERK通道特异性抑制剂UO126(20 nmol/L)和PI3K通道特异性抑制剂LY294002(20 nmol/L)分别作用于经血小板衍生生长因子PDGF-BB(10 ng/ml)处理的大鼠肝星状细胞(HSC)48 h,CCK8法检测HSC增殖活性,免疫化学染色法测定Ⅰ、Ⅲ型胶原合成,酶联免疫吸附法观察Ⅰ、Ⅲ型胶原分泌,Western blot测定ERK1/2、p-ERK1/2、AKT和p-AKT蛋白表达。     结果       PDGF-BB 10 ng/ml处理后,HSC增殖明显增加(0.139±0.009),丹参素能抑制PDGF-BB刺激大鼠HSC增殖的作用,并随丹参素浓度增加(0.062、0.125、0.250 mmol/L)细胞增殖受到的抑制作用越强(0.102±0.008、0.083±0.007、0.066±0.014,P<0.05),Ⅰ、Ⅲ型胶原合成及分泌均显著减少(P<0.05),p-ERK1/2和p-AKT蛋白表达均显著降低(P<0.05)。     结论       丹参素可通过抑制PDGF-BB诱导的HSC增殖和活化,同时抑制与肝纤维化密切相关的MAPK、PI3K途径中ERK、AKT蛋白的磷酸化,负性调控肝纤维化过程,其机制可能与抑制ERK1/2和PI3K信号转导通路有关。
Abstract:
Objective       To investigate the inhibitory role of salvianic acid A (Danshensu) in the proliferation, collagen typeⅠand Ⅲ synthesis and secretion, and ERK1/2 and PI3K expression in rat hepatic stellate cells (HSCs) stimulated by platelet derived growth factor-BB (PDGF-BB).      Methods       After rat HSCs were isolated and primarily cultured, they were treated with Danshensu at different concentration (0.250, 0.125, and 0.062 mmol/L), a potent tyrosine kinase inhibitor UO126 (20 nmol/L), or PI3K channel specific inhibitor LY294002 (20 nmol/L) for 1 h. After which, 10 ng/ml PDGF-BB was added into the culture medium. After 48 h treatment, cell proliferation was evaluated by cell counting Kit-8. Synthesis and secretion of collagen Ⅰand Ⅲ were detected by quantitative immunocytochemical assay and ELISA respectively. Expression of ERK1/2, p-ERK1/2, AKT and p-AKT in the cells was detected by Western blotting.       Results       After treated by PDGF-BB, the proliferation of HSCs was significant increased. Danshensu inhibited proliferation in HSC stimulated by PDGF-BB in a dose-dependent manner(P<0.05). Danshensu treatment resulted in significant decrease of synthesis and secretion of collagen Ⅰ and Ⅲ, and so did expression of p-ERK1/2 and p-AKT were decreased significantly(P<0.05).      Conclusion        Danshensu inhibits proliferation and activation of HSCs possibly by suppressing ERK1/2 and PI3K signal transduction pathway, which are involved in hepatic fibrosis.

参考文献/References:

呙琳琳, 戴立里, 唐静. 丹参素对PDGF-BB刺激下肝星状细胞的抑制作用[J].第三军医大学学报,2011,33(15):1610-1614.

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更新日期/Last Update: 2011-07-21