摘要
目的 观察肝卵圆细胞（hepatic oval cell,HOC）对肝纤维化（hepatofibrosis,HF）大鼠肝组织中细胞外信号调节蛋白（extracellular regulated protein kinases,ERK）和丝裂原激活蛋白激酶（mitogen activated protein kinase,P38MAPK）信号通路蛋白的影响.方法 SD大鼠以高脂低蛋白饲养、饮用10%乙醇,皮下注射40%CCl4,隔4 d注射一次,连续8周制备HF模型.HF大鼠采用胶原酶原位灌注法分离,percall纯化原代HOC.HOC悬液0.5 ml（1×109个细胞）经门静脉植入8周HF大鼠的肝脏内,分别于8、15、30d处死大鼠,HE和Masson染色观察HF病理组织学变化,Western blot 法检测肝组织ERK与P38MAPK信号通路蛋白的表达,同时检测ALB、FGF-3、c-kit、HNF-1α、PCNA表达.结果 病理组织学显示,HOC处理组大鼠HF被部分逆转,肝组织胶原纤维增生程度明显减轻,肝组织Ras、ERK、p-ERK、c-fos、c-jun、STAT3、ALB、FGF-3、PCNA蛋白表达显著下降（分别F=91.88,36.28,54.66,93.07,64.76,58.49,52.63,20.45,27.03,均P＜0.05）,而HNF-α1和c-kit表达上调（分别F=18.63,25.99,均P＜0.05）.结论 HOC抑制HF活化的ERK信号通路而改善肝纤维化程度,在HOC存在条件下p-P38并不激活c-fos、c-jun、STAT3、5表达,c-kit和HNF-1α表达增加,而肝组织结构损害程度明显减轻,肝纤维化程度明显改善.
Objective To observe the influence of hepatic oval cell （HOC） on the expression ERK and P38MAPK signaling pathway protein in liver tissue of murine experimental hepatofibrosis （HF）.Method SD rats were fed with 10% ethanol and food with high-fat and low-protein, and were injected subcutaneously with carbontetrachloride once every four days for 8 weeks to establish hepatic fibrosis. HOGs were isolated from male HF rats by collagenase porfusion of the liver. HF rats at 8th week were transplanted with 0. 5 ml HOC suspension medium at a density of 1 × 109 cell /ml via portal vein, and the rats were sacrificed at 8th, 15th, 30th day respectively. Histopathologic changes of liver tissues were observed by HE and Masson. The expression of ERK and P38MAPK signaling pathway protein were determined by Western blotting. Result Hepatofibrosis was reversed and the degree of hyperplasia fibrilcollagen in hepatic fibrosis rats decreased significantly by HOC transplantion. HOC down-regulated the protein expression of Ras, ERK,p-ERK, c-fos, c-jun, STAT3, ALB, FGF-3, PCNA （ F = 91.88,36.28,54.66,93.07,64.76,58.49,52.63,20.45 ,27.03, all P 〈 0.05 ）, up-regulated the protein expression level of HNF-α1, PDGF-Rβ significantly in liver tissues（F = 18.63,25.99,P 〈0.05）. Conclusions HOC improves the degree of hepatofibrosis through inhibiting hyperplasia of collagen fibril in liver tissue of hepatofibrosis rats. With the presence of HOC the expression of c-fos,c-jun,STAT3,5 was not activated by p-P38MAPK. The expression of c-kit and HNF-1α increased and that liver tissue injury alleviated, and hepatofibrosis was improved.
出处
《中华普通外科杂志》
CSCD
北大核心
2011年第1期52-57,共6页
Chinese Journal of General Surgery
基金
第四军医大学西京医院学科助推计划
关键词
肝细胞
肝硬化
细胞外信号调节激酶
丝裂原激活蛋白激酶类
Hepatocytes
Liver cirrhosis
Extracellular regulated protein kinases
Mitogenactivated protein kinases
