Zhu Yulin, Zhou Rongsheng, Yang Hui, Tan Jing, Zhang Xiaoqi, Liu Qining
Department of Anesthesiology, First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710061, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2012 Sep;32(9):1301-6.
To investigate the effect of pretreatment with ulinastatin on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats after 70% hepatectomy combined with ischemia-reperfusion injury.
A total of 120 normal male SD rats weighing 230-280 g were randomized into 3 groups (n=40), namely simple partial hepatectomy (PH) group, partial hepatectomy with ischemia-reperfusion (PHIR) group, and ulinastatin group. All the rats received resection of the left and middle liver lobes. In PHIR group, the remnant right lobes were subjected to blood flow occlusion for 30 min; in UTI group, the rats were given 50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant liver tissues were examined for regenerated liver weight, PCNA staining, TNF-α and IL-6, STAT-3, cyclin D1, and Cdk4 expressions.
The regenerated liver weight and PCNA positivity rates were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h after the reperfusion (P<0.05). In ulinastatin group, the levels of TNF-α and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1 and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h (P<0.05).
Ulinastatin can promote liver regeneration after major hepatectomy and ischemia-reperfusion injury, and the effect is possibly related with activation of IL-6/STAT-3 signal pathway, which promotes the synthesis of cyclin Dl-Cdk4 complex and hepatocyte proliferation.
探讨乌司他丁预处理对70%肝切除联合缺血再灌注损伤大鼠肝脏再生及肿瘤坏死因子-α/白细胞介素-6/信号转导和转录激活因子-3（TNF-α/IL-6/STAT-3）信号通路的影响。
将120只体重230 - 280 g的正常雄性SD大鼠随机分为3组（每组n = 40），即单纯部分肝切除术（PH）组、部分肝切除联合缺血再灌注（PHIR）组和乌司他丁组。所有大鼠均行左、中叶肝切除。在PHIR组中，残余右叶进行30分钟的血流阻断；在乌司他丁组中，大鼠在阻断前静脉注射50 000 U/kg乌司他丁，而在PH组中不进行血流阻断。再灌注后1、6、12、24和48小时，检测残余肝组织的再生肝重量、增殖细胞核抗原（PCNA）染色、TNF-α、IL-6、STAT-3、细胞周期蛋白D1（cyclin D1）和细胞周期蛋白依赖性激酶4（Cdk4）的表达。
再灌注后24小时和48小时，乌司他丁组的再生肝重量和PCNA阳性率显著高于PHIR组（P < 0.05）。在24小时和48小时时，乌司他丁组的TNF-α和IL-6水平显著降低，而IL-6水平以及STAT-3、cyclin D1和Cdk4 mRNA的表达以及cyclin D1和Cdk4蛋白的表达显著高于PHIR组（P < 0.05）。
乌司他丁可促进大肝切除及缺血再灌注损伤后的肝脏再生，其作用可能与激活IL-6/STAT-3信号通路有关，该通路促进cyclin Dl - Cdk4复合物的合成及肝细胞增殖。
