大鼠合并缺血再灌注损伤肝大部切除后Ki-67、Cyclin D1及TNF-α的表达

EXPRESSIONS OF Ki-67、CYCLIN D1 AND TNF-α IN RATS AFTER MAJOR HEPATECTOMY WITH ISCHEMIA REPERFUSION INJURY

目的探讨缺血再灌注损伤对残肝再生功能的影响及其作用机制。方法健康的雌性S-D大鼠随机分为两组即:单纯肝叶切除组(PH组)和缺血再灌注损伤状态下肝叶切除组(IR组)。分别取术前及术后0.5、6、12、24、48 h等时间点,应用全自动生化分析仪检测血清ALT、AST含量,通过免疫组化法检测残肝组织中K i-67和Cyc lin D1表达变化,采用放免法检测血清中TNF-α含量。结果IR组大鼠术后24 h内各检测点的血清AST、ALT值明显高于PH组(P<0.05);pH组大鼠肝细胞K i-67和Cyc lin D1表达在术后24 h达到峰值,且明显高于IR组,分别为6.13±1.33vs4.03±0.43,5.92±0.54vs3.97±0.45(P<0.05);术后0.5 h及6 h IR组大鼠的血清TNF-α表达量明显高于PH组,分别为7.06±1.71 pmol/Lvs4.66±0.87pmol/L,8.3±2.55 pmol/Lvs5.14±1.11 pmol/L(P<0.05)。结论缺血再灌注损伤会损害大鼠肝大部切除术后残肝再生功能,其作用机制可能与术后早期TNF-α持续过量表达有关。

Objective To investigated the effects of ischemia reperfusion injury on residual liver regeneration after major hepatectomy in rats and its mechanism. Methods Female Wistar rats were randomized into 2 groups： Group PH, rats subjected to 70% hepatectomy alone. Group IR, rats were subjected to 30 min of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion. At preoperative and 0. 5,6,12,24,48 h after operation serum AST and ALT activities were measured using a autoanalyzer, the expression of Ki-67and CyclinD1 were determined with immunohistochemical methods in remnant liver tissue , and the expressions of Serum TNF-α were measured with radioimmunoassay. Results The expressions of serum AST and ALT were significantly higher in IR rats than in group PH from 0. 5 - 24 h after 70% pH （P 〈 0. 05 ）. The expression of Ki-67and CyclinD1 reached the peak at 24 h after PH in group Ptt, and it were significantly higher compared with those of group IR（6.13± 1.33 vs 4.03 ± 0. 43,5.92 ± 0. 54 vs 3.97 ±0. dS） （P 〈0. 05）. At 0. 5 h and at 6 h after 70 % PH the expression levels of TNF-α was significantly higher in IR rats than ingroup pH（7. 06 ±1. 71 pmol/L vs 4. 66 ± 0. 87 pmol/L,8.3 ±2.55 pmol/Lvs5.14±l, ll pmol/L）（P〈0. 05）.Conclusion Ischemia reperfusion injury impairs the residual liver regeneration after major hepatectomy in rats. The increased expression of TNF-α in the early stage after hepatectomy may be the causes of the inhibited liver regeneration.