枯否氏细胞在大鼠肝切除后肝再生中的作用研究

Role of Kupffer cells in rat liver regeneration

目的 实验通过药物灭活枯否氏细胞后 ,观察大鼠肝再生的情况 ,探讨枯否氏细胞在大鼠肝再生调控中所起的作用。方法 切除 6 8%肝脏 ,制备大鼠肝再生模型。实验分对照组、氯化钆 (GdCl)组。术后比较再生肝的重量 ,采用放射免疫法测定各实验组血中肿瘤坏死因子 α(TNF α)浓度 ,原位杂交检测TNF αmRNA基因表达及分布 ,免疫组化LSAB法检测增殖细胞核抗原 (PCNA)蛋白的表达。结果 GdCl组在肝切除后 72h再生肝的重量高于对照组 (P <0 .0 5 ) ,血中TNF α浓度在肝切除后 2 4h内各个时段均明显高于对照组 (P <0 0 5 ) ,PCNA蛋白在肝切除后 3h即有表达 ,48h达高峰 ,表达明显高于对照组(P <0 0 5 )。结论 枯否氏细胞被GdCl灭活后并不抑制大鼠肝再生 ,反而增强大鼠肝再生。说明枯否氏细胞在肝再生中起有双重作用 。

Objective To study the effects of Kupffer cells on rat liver regeneration by Kupffer cell depletion.Methods The rat model of liver regeneration was made by partial(68%) hepatectomy(PH). 96 rats were divided into two groups:the normal group,and the group injected with gadoliniam chloride(GdCl) via tail vein. The weight of the remnant liver of each rat in the GdCl-treated group was compared with that in the normal group.Serum tumor necrosis factor-α(TNF-α) concentrations were determined by radioimmunoassay.TNF-α mRNA gene expressions in liver cells were detected by in situ hybridization.The synthesis and distribution of proliferating-cell nuclear antigen(PCNA) protein in liver tissue were examined by immunohistochemical and morphometric methods.The results were given as mean±SE.Data were analyzed using analysis of variance.Results The weight of the remnant liver was significantly increased at 72 h after PH in the GdCl-treated group.Serum TNF concentrations were higher in the GdCl-treated group than in the normal group at each time point after PH(P<0.05).Expressions of PCNA in GdCl-treated rats were noted 3 h post-PH and were greater than those in controls at 24 h and 48 h post-PH(P<0.05).Conclusions Despite depleting kupffer cells,GdCl pretreatment leads to significantly increased rat liver regeneration.These results underscore the importance of Kupffer cells in the regulation of rat liver regeneration.