Objectives To observe the expressions of discoidin domain receptor 2 (DDR2) in different phases of alcoholic liver fibrosis (ALF) in a rat model and to study the possible association between DDR2 and collagen deposition in ALF. Methods After an ALF rat model was established by alcohol gastrogavage and an olive oil diet, the liver histopathology was observed in different phases of the development of fibrosis. The expressions of DDR2 mRNA and protein were also detected by RT-PCR and Western blot respectively to make a dependability analysis with the index of ALF. Results (1) The expressions of DDR2 mRNA and protein increased gradually along with ALF aggravation. In the normal control group, they were respectively 1.023±0.132 and 0.321±0.027; in the model 1 group (week 12) they were 3.644±1.686, 0.476±0.046; in the model 2 group (week 16) they were 8.337±2.387, 0.738±0.057; and in the model 3 group (week 20) they were 15.730±4.569, 0.997±0.049. The differences of DDR2 mRNA (F=21.74, P<0.01) and protein (F =10.38, P<0.01) among these four groups were significant. (2) The expressions of DDR2 had a positive correlation with collagen type Ⅰ, Ⅲ, Ⅳ contents and the serum index of ALF, especially with type Ⅲ and Ⅳ collagen and serum hexadecenoic acid. Conclusion The expression of DDR2 in this ALF model correlates closely with collagen deposition in the liver, suggesting that it may play an important role in ALF pathogenesis.%目的 观察盘状结构域受体2(DDR2)在大鼠酒精性肝纤维化不同病理阶段的表达情况,揭示DDR2在酒精性肝纤维化发生、发展中的作用.方法 橄榄油拌平衡饲料喂养大鼠的基础上给予60%(V/V)白酒胃内灌注,制备酒精性肝纤维化模型,分别于12、16、20周末观察肝脏病理学改变,并检测血清学指标和肝纤维化指标,荧光定量-PCR和Western blot检测肝组织DDR2基因和蛋白表达并与各项酒精性肝纤维化评价指标进行相关性分析.结果 (1)白酒灌胃后DDR2 mRNA和蛋白表达量随造模时间延长而增加,对照组DDR2 mRNA和蛋白表达分别为1.023±0.132、0.321±0.027,模型1组为3.644±1.686、0.476±0.046,模型2组为8.337±2.387、0.738±0.057,模型3组为15.730±4.569、0.997±0.049,四组之间DDR2 mRNA水平(F=21.74,P<0.01)及蛋白质表达(F=10.38,P<0.01)差异有统计学意义.(2)相关性分析显示酒精性肝纤维化形成过程中,DDR2与Ⅰ、Ⅲ、Ⅳ型胶原面积及血清透明质酸、层黏连蛋白、Ⅲ型前胶原、Ⅳ型胶原蛋白水平等均呈显著正相关,其中与Ⅲ型胶原、透明质酸、Ⅳ型胶原蛋白关系最为密切.结论 随酒精性肝纤维化进展,DDR2表达呈时间依赖性,提示其在酒精性肝纤维化的发生和进展中发挥重要作用.
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