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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.
Objective: To investigate the effect of rapamycin on the expression of HMGB1 in hepatic tissue of rats with acute hepatic injury by inhibiting JAK / STAT pathway. Methods: Acute liver injury (ALI) model was duplicated by D-Galn / LPS. Rats were randomly divided into normal control group (n = 30), ALI group (n = 30) and STAT inhibitor rapamycin group (n = 30). Western blot method was used to determine the liver tissue HMGB41 protein, automatic biochemical analyzer measured liver function. Results: The expression of HMGB1 in ALI group was significantly higher than that in control group (1.00 ± 0.02) at 24.72 h (3.12 ± 0.06, 3.9 ± 0.08, 2, .83 ± 0.04, t values were 16.01,3.86,10.46, respectively, P <0.01), serum alanine aminotransferase (ALT) 6 and 24 h had two peaks, and 24 h peak is higher than 6 h. Compared with ALI group, HMGB1 protein expression in RPM pretreatment group was significantly inhibited at 24-72h (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 values were 20.11, 41.90, 26.02, all P <0.01), ALT at 24,48,72 h Also decreased to some extent (P <0.01). ALT and HMGB1 was positively correlated (r = 0.741, P <0.01). Conclusion: Inhibition of JAK / STAT can down-regulate the expression of HMGB1 in liver tissue and help to alleviate the acute liver injury induced by D-Galn / LPS.