德都红花-7味散对大鼠肝再生过程的双向调节作用机制研究

Bidirectional regulation and mechanism of Deduhonghua-7 powder on liver regeneration process in rats

目的探讨在肝再生过程中德都红花-7味散对酪氨酸激酶(JAK)/信号转导及转录激活因子(STAT)信号通路的影响。方法按照随机数字表法将SD大鼠分为4组:假手术组、模型组、阳性对照组和实验组,每组20只。阳性对照组灌胃护肝片(0.28 g·kg^-1),实验组灌胃德都红花七味散(0.6 g·kg^-1)。大鼠部分肝切除术(PHT)法建立肝再生模型,于PHT后6和48 h各组取大鼠10只,计算肝再生率;酶联免疫吸附法检测肝匀浆JAK1、STAT3含量,蛋白质印迹法检测肝组织JAK1、STAT3蛋白表达。结果在PHT后6 h,模型组、阳性对照组和实验组的肝再生率分别为(1.92±0.44)%,(6.36±0.27)%和(2.79±0.27)%,实验组与模型组比较,差异有统计学意义(P<0.05);实验组与阳性对照组比较,差异有统计学意义(P<0.05)。在PHT术后48 h,假手术组、模型组、阳性对照组和实验组的JAK1含量分别为(2.34±0.13),(2.78±0.19),(2.09±0.24)和(1.77±0.15)U·mL^-1;这4组的STAT3含量分别为(22.21±1.15),(26.56±2.26),(19.54±0.22)和(20.88±2.46)ng·mL^-1;这4组的JAK1蛋白表达分别为0.31±0.02,0.60±0.03,0.22±0.02和0.21±0.04;这4组的STAT3分别为0.80±0.03,0.93±0.02,0.43±0.03和0.52±0.02。上述指标:模型组与假手术组比较,差异均有统计学意义(均P<0.05);实验组与模型组差异均有统计学意义(均P<0.05)。结论德都红花-7味散通过下调JAK1、STAT3蛋白表达,阻断JAK1/STAT3细胞信号传导通路,在肝再生过程中起到是双向调节作用,在促进肝再生率的同时,防止过度增殖。

Objective To investigate the effect of Deduhonghua-7 powder on the Janus activated kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway during liver regeneration in rats.Methods The SD rats were divided into four groups:normal group,model group,positive control group and experimental group,with 20 rats in each group.Gavage Hugan tablets for the positive control group(0.28 g·kg^-1),intragastric administration of Deduhonghua-7 powder(0.6 g·kg^-1).Meanwhile,the liver regeneration model was established by partial hepatectomy(PHT)method.At 6 h and 48 h after partial hepatectomy,10 rats were taken from each group to calculate the liver regeneration rate.The contents of JAK1 and STAT3 in liver homogenate were detected by enzyme linked immunosorbent assay.Expressions of JAK1 and STAT3 proteins in liver were detected by Western blot.Results The liver regeneration rate of model group,positive control group and experimental group at 6 h after PHT were(1.92±0.44)%and(6.36±0.27)%,(2.79±0.27)%;the difference between the experimental group and the model group was statistically significant(P<0.05),and the difference between the experimental group and the positive control group was statistically significant(P<0.05).The JAK1 content in sham operation group,model group,positive control group,and experimental group were(2.34±0.13),(2.78±0.19),(2.09±0.24)and(1.77±0.15)U·mL^-1;the STAT3 content in the 4 groups were(22.21±1.15),(26.56±2.26),(19.54±0.22)and(20.88±2.46)ng·mL^-1;the JAK1 protein expression in the 4 groups were 0.31±0.02,0.60±0.03,0.22±0.02 and 0.21±0.04;the STAT3 protein expression in the 4 groups were 0.80±0.03,0.93±0.02,0.43±0.03 and 0.52±0.02.The differences of the factors between the model group and the sham operation group were statistically significant(all P<0.05),and the differences of the factors between the experimental group and the model group were statistically significant(all P<0.05).Conclusion By down-regulating the expression of JAK1 and STAT3 proteins,the JAK1/STAT3 signaling pathway was blocked by Deduhonghua-7 Powder.It plays a bidirectional regulation role in the process of liver regeneration,promoting the rate of liver regeneration and preventing excessive proliferation.