脓毒症大鼠肝组织凝溶胶蛋白表达变化及血必净注射液干预的影响

Expression change of hepatic gelsolin and potential effect of Xuebijing injection in septic rats

目的 观察脓毒症大鼠肝组织凝溶胶蛋白（GSN）表达规律及中药血必净注射液干预的影响. 方法雄性Wistar大鼠104只,按随机数字表法分为正常对照组（8只）、假手术组（32只）、盲肠结扎穿孔（CLP）组（32只）、血必净组（32只）,后两组采用CLP制备脓毒症大鼠模型.血必净组于术后2,12,24,36,48,60 h静脉注射血必净注射液,每次剂量4 ml/kg.分别于术后6,12,24,72 h处死大鼠留取血和肝组织标本,检测肝功能生化指标和肝组织GSN、Gc球蛋白含量及GSN mRNA表达水平. 结果与正常对照组（2.28±0.34）ng/mg和假手术组比较,CLP组大鼠肝组织GSN含量显著下降（P＜0.05）,12 h其含量最低,为（1.42±0.50）ng/mg;而肝组织GSN mRNA表达于CLP后6 h即明显上调,72 h仍高于假手术组（1.203±0.053比1.030±0.084,P＜0.05）;CLP组6～72 h肝组织Gc球蛋白含量较正对照常组、假手术组均有不同程度的升高（P＜0.05）.血必净治疗6～72 h肝组织GSN含量均显著高于CLP组（P＜0.05）,6,12,24 h血清ALT、AST水平则明显低于CLP组（P＜0.05）.血必净干预对肝组织GSN mRNA表达和Gc球蛋白水平均无明显影响（P＞0.05）.结论 脓毒症时肝组织GSN含量持续降低,血必净可通过增加动物肝组织GSN含量,减轻脓毒症所致的肝功能损伤.

Objective To investigate the expression changes of hepatic gelsolin （GSN） and the potential effect of traditional Chinese medicine Xuebijing injection in septic rats. Methods A total of 104 male Wistar rats were randomly divided into four groups, ie, normal control group （n = 8）, sham operation group （n = 32）, cecal ligation and puncture group （CLP group, n = 32） and Xuebijing treatment group （n = 32）. The sepsis animal models in the last two groups were developed by CLP. In Xuebijing treatment group, animals were treated intravenously with Xuebijing injection （4 ml/kg） at 2, 12, 24,36, 48 and 60 hours after operation, respectively. Animals were sacrificed respectively at 6, 12, 24, and 72 hours after operation to harvest blood and hepatic tissue samples. Markers of liver function, contents of GSN and Gc globulin and expression of GSN mRNA in the liver tissues were detected. Results Compared with normal control group and sham operation group, hepatic GSN content was decreased significantly at various intervals in CLP group （P 〈 0. 05）, which reached the lowest value of （1.42 ±0.50） ng/mg at 12 hours. Meanwhile, expression of GSN mRNA in the liver was markedly enhanced at six hours after CLP and remained a high value until 72 hours, compared with the sham operation group （1.203±0.053 vs 1.030 ±0.084, P 〈0.05）. Similarly, the hepatic Gc globulin contents was increased in the CLP group compared with the normal control group and sham operation group （P 〈 0.05）.After treatment with Xuebijing injection, the hepatic GSN contents at 6-72 hours was increased gradually while serum ALT and AST levels at 6, 12 and 24 hours were reduced significantly in comparison to the CLP group （P 〈 0.05）. Nevertheless, treatment with Xuebijing injection showed no marked effect on hepatic GSN mRNA expression and Gc globulin release （P 〉 0.05）. Conclusions Hepatic GSN contents are persistently reduced in the development of sepsis and treatment with Xuebijing injection can markedly attenuate acute liver injury through increasing GSN contents in severe sepsis.