摘要
目的：探讨雷帕霉素抑制JAK/STAT通路对急性肝损伤大鼠肝组织HMGB1表达的影响．方法：采用D-Galn/LPS复制急性肝损伤(ALI)模型．大鼠随机分为正常对照组(n=30)、ALI组(n=30)、STAT抑制剂雷帕霉素(RPM)处理组(n=30)．用Western blot方法测定肝组织HMGB41蛋白,全自动生化分析仪测定肝功能指标．结果：与正常对照组HMGB1表达水平(1．00±0．02)相比,ALI组24．72 h HMGB1表达显著升高(3．12±0．06,3．9±0．08,2．83±0．04,t值分别为16．01,3．86,10．46,均P＜0．01),血清丙氨酸转氨酶(ALT)6和24 h有两个峰值,且24 h峰值高于6 h．与ALI组相比,RPM预处理组24-72h HMGB1蛋白表达均显著抑制(1．67±0．05 vs 3．12±0．06：1．93±0．06 vs 3．9±0．08：1．47±0．04 vs 2．83±0．04：t值分别为20．11,41．90,26．02,均P＜0．01),ALT在24,48,72 h也均有不同程度下降(P＜0．01)．ALT与HMGB1呈正相关(r=0．741,P＜0．01)．结论：抑制JAK/STAT可明显下调肝组织中HMGB1蛋白表达,并有助于减轻D-Galn/LPS所致的急性肝损伤．
AIM： To investigate the effect of rapamycin （RPM） on the expression of high-mobility group box 1 （HMGB1） in rats with acute liver injury （ALI） by inhibiting Janus kinase/signal transducer and activator of transcription pathway.
METHODS： Wistar rats were randomly divided into normal control group （n=30）, ALI group （n=30） and RPM treatment group （n=30）. ALI was induced by intraperitoneal administration of D-Galactosamine/lipopolysaccharide （D-Galn/LPS）. The animals in each group were sacrificed at different time points to collect the blood and hepatic tissue samples for the detection of alanine aminotransferase （ALT） level and HMGB1 expression, respectively. RESULTS： In comparison with that in the normal controls （1.00±0.02）, HMGB1 expression was significantly increased in liver tissues 24, 48 and 72 h after ALI （3.12±0.06, 3.9±0.08, 2.83±0.04, respectively, t= 16.01, 3.86, 10.46, all P〈0.01）, and serum ALT levels were markedly elevated. The expression of HMGB1 in liver tissues was dramatically inhibited 24, 48 and 72 h after RPM treatment as compared with that in ALI group （1.67± 0.05 vs 3.12±0.06; 1.93±0.06 vs 3.9±0.08; 1.47±0.04 vs 2.83±0.04; t=20.11, 41.90, 26.02, all P〈0.01）. In addition, serum ALT levels were also markedly reduced during 24-72 h after RPM treatment （P 〈 0.01）. HMGB1 expression was positively correlated with ALT level （r=0.741, P〈0.01）.
CONCLUSION： The activation of JAK/STAT pathway may be involved in the up-regulation of HMGB1 expression in ALI. RPM treatment can markedly down-regulates HMGB1 expression and attenuates ALI.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第19期1916-1920,共5页
World Chinese Journal of Digestology
