丹参素对STAT1、PPARγ和HGF在糖尿病小鼠肝脏中表达的影响

Effect of Danshensu on expression of STAT1,PPARγ and hepatocyte growth factor in the liver of mice with streptozotocin-induced diabetes

目的观察丹参素对链脲佐菌素(STZ)诱导的糖尿病小鼠肝脏组织中信号转导和转录活化因子1(STAT1)、过氧化物酶体增殖物激活受体γ(PPARγ)以及肝细胞生长因子(HGF)表达的影响,探讨其对糖尿病小鼠肝脏保护作用的机制。方法 60只健康雄性C57BL/6小鼠中随机选取10只作为正常对照组,剩余50只小鼠按200 mg/kg一次性腹腔注射STZ 500mg,72 h后尾尖取血测空腹血糖,血糖值大于20 mmol/L为糖尿病小鼠。40只糖尿病小鼠随机分为糖尿病模型组,丹参素低剂量组(15 mg/kg)、中剂量组(30 mg/kg)、高剂量组(60 mg/kg)。丹参素组小鼠1次/d灌胃给药,连续给药12周,末次给药12 h后检测空腹血糖、胰岛素、糖基化血红蛋白(GHb)的水平,及天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平。用蛋白质印迹分析法检测小鼠肝脏组织中STAT1、PPARγ和HGF蛋白的表达。结果 (1)与正常对照组相比,糖尿病模型组及丹参素组的血糖及GHb水平均增高(P<0.01),胰岛素水平降低(P<0.01),丹参素各剂量组间血糖、胰岛素及GHb水平差异无统计学意义。(2)糖尿病模型组血清AST、ALT水平较正常对照组升高(P<0.05);丹参素组血清AST、ALT水平较糖尿病模型组下降(P<0.05);丹参素各剂量组间AST、ALT水平差异无统计学意义。(3)糖尿病模型组小鼠肝组织中STAT1表达高于正常对照组(P<0.01),而PPARγ和HGF的表达则降低(P<0.01);与糖尿病模型组比较,丹参素组的小鼠肝脏组织中PPARγ和HGF的表达上调(P<0.01),STAT1表达减少(P<0.01),且呈剂量依赖性。结论丹参素对糖尿病肝损害的保护作用可能与上调糖尿病小鼠肝脏组织中PPARγ和HGF的表达,抑制STAT1介导的炎症反应有关。

Objective To study the effect of Danshensu on the expressions of signal transducer and activator of transcription 1（STAT1）,peroxiome proliferators-activated receptor-γ（PPAR-γ） and hepatocyte growth factor（HGF） in streptozotocin-induced diabetic mice,and to assess its protective effect on the liver of mice.Methods Diabetic mice were induced by intraperitoneal injection of 500 mg streptozotocin（200 mg/kg）.Then the diabetic mice were randomly divided into four groups： diabetic model group,low-dose Danshensu（15 mg/kg） group,middle-dose Danshensu（30 mg/kg） group and high-dose Danshensu（60 mg/kg） group,with 10 mice in each group.Danshensu（sodium salt of Danshensu） was administered intragastrically once a day for 12 weeks.Ten normal mice were taken as controls.The fasting blood glucose,insulin and glycosylated hemoglobin（GHb） levels were examined at 12 h after the last administration of the drug.The aspartate transaminade（AST） and alanine transaminade（ALT） levels in sera drawn from inner canthus were determined by automatic biochemical analyser.Western blotting analysis was used to examine the expression of STAT1,PPARγ and HGF in the liver tissues.Results（1） Compared with control group,the diabetic model group and Danshensu groups had significantly higher blood glucose and GHb levels（P0.01） and significantly lower insulin level（P0.01）.There were no significant differences between the three Danshensu groups concerning the three parameters.（2） The levels of AST and ALT in diabetic model group were significantly higher than those in the control group（P0.05）;their levels in the three Danshensu groups were significantly lower than those of the diabetic model group（P0.05）;there were no significant differences among the three Danshensu groups.（3） The expression of STAT1 in diabetic model group was significantly higher and the expression of PPARγ and HGF was significantly lower than those in control group（P0.01）.Compared with the diabetic model group,PPARγ and HGF expression in the liver tissues was significantly increased and STAT1 expression was significantly decreased in a dose-dependent manner with Danshensu（P0.01）.Conclusion The protective effect of Danshensu on liver tissues in streptozotocin-induced diabetic mice might be associated with increase of PPARγ and HGF expression and decrease of STAT1 expression.