Abstract: 【Abstract】 Objective〓To study the effect of histone preconditinoning on liver function in biliary obstruction rats. Methods〓104 Wistar rats were randomized into 4 group, normal group (group A), sham operation group (group B), bile duct ligation group (group C) and the His group (group D, (200 μg/kg of histone proteins was administered intraperitoneally 24 hr before subjected to BDL). After the surgery, blood samples and live tissue specimens were collected at the time points of 0 h, 12 h, 24 h, 48 h and 72 h. Serum ALT, TB and DB levels were detected. Histological changes of liver tissues were analyzed. Serum IL-6, TNF-α and His levels were detected by ELISA. The mRNA expression levels of TLR-4 in liver Kupffer cells was examined by reverse transcription polymerase chain reaction (RT-PCR). Results〓The pathological scores in C group were higher than those of A and B group (P<0.01) and D group (P<0.05). The serum IL-6 and TNF-α levels in C group were higher than those of B group and group D at each time (P<0.01, P<0.05). Compared to B group, the TLR4 mRNA expression in Kupffer Cells were increased in C group with significant difference (P<0.01). In D group, the mRNA expression levels of TLR4 in Kupffer Cells were lower than those of C group at each time point (P<0.05). Conclusion〓In our study, histone preconditioning protected against liver injury in biliary obstruction rats. The levels of IL-6 and TNF-α were suppressed by activate the TLR4 pathway in Kupffer cells, local and systemic inflammatory response were suppressed.

Key words: Histone, Biliary obstruction, Liver function

摘要： 【摘要】〓目的〓探讨组蛋白预处理对胆道梗阻大鼠肝功能的影响。方法〓104只大鼠随机分成4组:正常组(A组)、假手术组(B组)、胆管结扎组(C组)和His预处理组(D组,胆管结扎前24 h腹腔注射组蛋白(200 μg/kg)。设A组为0时相,B、C、D组分为术后12、24、48、72 h 4个时相,每个时相8只。留取血样和肝组织标本,检测血清ALT、DB、TB水平,观察肝组织病理学改变。ELISA检测血清IL-6和TNF-α水平,RT-PCR方法检测Kupffer细胞TLR4 mRNA表达水平。结果〓C组各时相肝组织病理评分高于A和B组(P<0.01)和D组(P<0.05)的相应时相。C组血清IL-6和TNF-α水平术后逐渐升高,高于B组相应时相(P<0.01);D组各时相血清IL-6和TNF-α水平低于C组,(P<0.05)。C组Kupffer细胞Toll-样受体4 mRNA(TLR4 mRNA)表达术后逐渐升高,高于A和B组相应时相(P<0.01);D组各时相Kupffer细胞TLR4 mRNA表达低于C组(P<0.05)。结论〓对胆道梗阻大鼠给予组蛋白预处理,可以减轻肝功能损害;通过激活Kupffer细胞TLR4减少炎症介质IL-6、TNF-α产生,抑制局部及全身的炎症反应。

关键词: 组蛋白, 胆道梗阻, 肝功能