急性胰腺炎肝巨噬细胞表达的FasL在肝损伤中的作用

The role of Kupffer cell-expressed FasL in liver injury during acute pancreatitis

目的:探讨肝巨噬细胞表达的Fas配体(FasL)在实验性急性胰腺炎(AP)肝损伤中的作用。方法:建立AP小鼠模型。雄性ICR小鼠30只,随机分为5组,每组6只,其中一组为对照组,腹腔注射0.1m l等渗盐水,4 h后心脏穿刺抽血,并处死小鼠留取标本;另4组均腹腔注射雨蛙素50μg/kg,每4 h注射1次至24 h,分别在4、8、16和24 h心脏穿刺抽血,并处死小鼠留取标本。用自动化生化仪检测血清ALT、AST、LDH和AMY的浓度,用ELISA试剂盒检测血清FasL浓度,用W estern b lot检测肝FasL蛋白的表达。结果:雨蛙素诱导的小鼠AP组与对照组相比,各个检测时间点血清AST、ALT、LDH、AMY水平明显增加。在4、8、16和24 h时AP组血清FasL浓度为(532.17±46.92)、(496.73±32.62)、(485.57±18.31)和(448.08±26.44)pg/m l,均显著高于对照组(80.34±6.81)pg/m l,AP组各检测时间点肝FasL蛋白表达也增加,与对照组相比,差异有显著统计学意义(P<0.01)。结论:AP通过上调肝巨噬细胞表达的FasL介导肝损伤。

Objective： To explore the role of Kupffer cell-expressed liver Fas ligand （FasL） in liver injury during acute pancreatitis （AP）. Methods： Thirty male ICR mice were randomly and equally divided into 4 AP model groups, induced by intraperitoneal injection of cerulein （50 μg/kg IP q4 h for 24 h）, and a control group, receiving 0.1 ml of 0.9% NaCl intraperitoneally. Serum was harvested by heart puncture 4 h after the 0.9% NaCl injection and 4, 8, 16, and 24 h after the first cerulein injection and all the mice were sacrificed for getting samples. The levels of serum AST, ALT, LDH and AMY were measured with an automated analyzer, the concentration of FasL determined by enzymelinked immunosorbent assay （ELISA） , and the expression of the FasL protein in the liver detected by Western blot. Results ： The levels of AST, ALT, LDH and AMY were markedly increased, and the serum concentration of FasL in the 4, 8, 16 and 24 h groups of the AP models were （532.17 ± 46.92）, （496.73 ±32.62）, （485.57± 18.31 ） and （448.08 ± 26.44） pg/ml, respectively, significantly higher than that in the control, which was （80.34±6.81 ）pg/ml. The expression of the FasL protein in the liver was obviously up-regnlated in all the model groups, with statistically significant difference from the control （P 〈 0.01 ）. Conclusion： AP induces liver injury by up-regnlating Kupffer cell-expressed FasL.