IL-6/STAT3与冷保存大鼠部分肝移植肝再生的关系

Relationship of IL-6/STAT3 with liver regeneration of partial grafts after cold preservation in rats

目的探讨冷保存对大鼠部分肝移植术后肝再生的影响及IL-6/STAT3与其的关系。方法实验分为Ⅰ组(肝切除组)、Ⅱ组(冷保存1h部分肝移植组)和Ⅲ组(冷保存8h部分肝移植组)。观察比较各组术后1、6、12、24、48、72、168h肝再生率、肝组织TNF-α、IL-6含量及增殖细胞核抗原(PCNA)、STAT3表达。结果Ⅰ组、Ⅱ组术后肝再生迅速,至术后第7天时分别接近和超过原来肝脏大小,Ⅲ组术后2～3d大鼠肝再生率较Ⅰ组、Ⅱ组明显偏低(P<0.05)。术后12h内Ⅰ组、Ⅱ组肝组织TNF-α、IL-6水平明显高于Ⅲ组(P<0.05)。Ⅰ组、Ⅱ组TNF-α、IL-6于术后12h达高峰,后逐渐下降;而Ⅲ组24h达高峰,此后一直维持较高水平。Ⅰ组、Ⅱ组PCNA表达于术后12～24h达高峰;Ⅲ组术后12h内PC-NA表达明显低于其余两组(P<0.05),48h才达高峰,但至第7天仍有较多表达。Ⅰ组、Ⅱ组术后1hSTAT3表达最多,以后逐渐下降,7d后表达基本消失。Ⅲ组STAT36h才出现表达,12h达高峰,7d时仍有较多表达。结论长时间冷保存降低了部分肝移植术后的肝再生能力,TNF-α、IL-6/STAT3的早期异常可能是长时间冷保存肝再生受损的主要原因之一。

Objective To evaluate the effect of different cold preservation time on liver regeneration after partial liver transplantation in rats, and study the role of IL-6/STAT3. Methods SD rats were divided into 3 groups： group Ⅰ underwent liver resection, group Ⅱ received preservation and group Ⅲ received partial partial liver transplantation after one-hour cold liver transplantation after 8-hour cold preservation. Radioimmunoassay was used to measure the levels of TNF-α and IL-6 in liver tissues. The protein expressions of PCNA and STAT3 were assessed by immunohistochemical staining in paraffin sections. The liver regeneration ratio and the expressions of the proliferative cell nuclear antigen （PCNA） and STAT3 were compared among three groups at 1, 6, 12, 24, 48, 72 and 168 h after operation. Results The remnant liver in group Ⅰ and grafts in group Ⅱ grew rapidly; The regeneration ratio in group Ⅲ was significantly lower than that in group Ⅰ and group Ⅱ during postoperative day 2 to 3 （P 〈 0.05 ）. The levels of TNF-α and IL-6 in group Ⅰ and group Ⅱ were markedly higher than those in group Ⅲ in postoperative 12 h （P 〈 0.05 ）. The maximum levels of TNF-α and IL-6 appeared at postoperative 12 h in group Ⅰ and group Ⅱ, at 24 h in grouplll. PCNA expressions in group Ⅰ and group Ⅱ were increased and reached the peak value at postoperative 24 h. PCNA expressions in group Ⅲ were markedly lower than groups Ⅰ and Ⅱ during postoperative 12 h （P 〈0.05）, and reached the peak at 48 h. STAT3 expression reached the peak at postoperative 1 h in groups Ⅰ and Ⅱ, then decreased gradually to undetectable at postoperative day 7. In group Ⅲ, STAT3 expressions were detected at 6 h and reached the peak at postoperative 12 h, still more at 7 d. Conclusion Longer cold preservation time leads to more impairment of the regenerative ability of liver after partial liver transplantation. The abnormal changes of TNF-α, IL-6 and STAT3 in the early period of regeneration may be the main mechanism for impaired partial graft regeneration after long-time cold preservation.