CXCR7在急性肝衰竭大鼠肝组织中的表达及意义

Dynamic Expressions of CXCR7 in Rats with Acute Hepatic Failure and Its Significance

目的探讨急性肝衰竭(acute liver failure,ALF)大鼠肝组织内趋化因子受体7(chemokine acceptors,CXCR7)的表达变化及意义。方法 36只雄性SD大鼠随机分为正常对照组和急性肝衰竭(ALF)组,ALF组同时腹腔注射D-氨基半乳糖(D-galactosamine,D-GalN)和脂多糖(D-galactosamine,LPS)诱导模型建立,分别于注射后2、6、12、24、48h留取血清及肝组织;采用HE染色,光学显微镜下观察肝组织病理变化;采用RT-PCR、Western blot法检测CXCR7 mRNA及CXCR7蛋白质表达水平;同时检测血清ALT、AST水平;统计处理采用LSD检验和Dunnet's T检验。结果 ALF组24、48h时肝组织病理呈现大量炎性细胞浸润和明显坏死;ALF组血清ALT、AST水平于24h达高峰且分别明显高于正常组(4670.667±372.436U/L、30.667±3.670U/L;4930.333±81.158U/L、67.667±8.140U/L,P<0.01);在2、6、12、24、48h时,ALF组CXCR7 mRNA与β-肌动蛋白(β-actin)吸光度比值分别为1.106±0.017、1.231±0.014、1.249±0.013、1.159±0.014、1.095±0.028,各时间点与正常组比较差异均有统计学意义(P<0.05);CXCR7蛋白与GAPDH灰度值比值分别为0.520±0.011、0.536±0.007、0.587±0.005、0.712±0.004、0.579±0.098,各点与正常组比较差异均有统计学意义(P<0.05)。结论成功诱导ALF大鼠模型建立,ALF时CXCR7mRNA及CXCR7蛋白质表达可能在肝组织损伤过程中发挥重要作用。

Objective To explore the dynamic expressions of CXCR7 in rats with acute hepatic failure（ALF） and its significance after building the ALF model. Methods Thirty - six male Sprague - Dawley （SD） rats were randomly divided into normal group and model group（ALF group）. The rat models were established by intraperitoneal injection of D -galactosamine（ D- Gal） ± Lipopolysaccharide （LPS）. At 2,6,12,24 and 48 h time point after injection, the serum were used to detect ALT and AST. The liver pathologic changes were observed with HE staining by microscope. The mRNA expressions of CXCRTmRNA were detected by reverse transeriptase polymerase chain reaction（ RT - PCR） and CXCR7 were detected by Western blot. Results In ALF group,The liver pathologic changes were most serious at 24h and 48h. The serum levels of ALT and AST were significantly increased at 24h compared to those in normal group （4670. 667 ± 372. 436U/L,30. 667 ± 3. 670U/L;4930. 333 ± 81. 158U/L,67. 667 ± 8. 140U/L,P 〈0.01 ） ,respectively. While the CXCR7 mRNA/β -actin absorbance ratios at 2,6,12,24 and 48h after D -GaIN and LPS challenge were 1. 106 ± 0. 017,1.231 ± 0. 014,1. 249 ±0.013, 1. 159 ± 0. 014,1. 095 ± 0. 028. The expression of CXCR7 were significantly increased compared to those in normal group （ F = 1687. 386, 4157. 921,4684. 103,2973. 799,2127. 463, P 〈 0.05 ） , respectively, while the CXCRT/GAPDH gray level ratios were 0. 520 ± O. 011, 0. 536 ± 0. 007,0. 587 -± 0. 005,0. 712 ± 0. 004,0. 579 ± 0. 098. The expression of CXCR7 was significantly increased compared to those in normal group （F=90.740,146.950,350.609,1174.296,921.838,P〈O.05）. Conclusion The rat model of ALF was established suc- cessfully by intraperitoneal injections of D - Gal and LPS. The expression of CXCR7mRNA and CXCR7 plays an important role in D - Gal and LPS -induced liver injury.