健脾清化方对2型糖尿病大鼠基因表达谱及信号通路的影响

Effect of Jianpi Qinghua Recipe( 健脾清化方) on Gene Expression Profile and Signal Pathway of Type 2 Diabetes Mellitus Rats

目的从基因转录水平角度探讨健脾清化方治疗2型糖尿病的可能作用机制。方法 50只Wistar大鼠随机选择40只建立2型糖尿病大鼠模型,另外10只大鼠作为对照组。造摸成功的30只大鼠随机分为模型组和健脾清化方组,每组15只。健脾清化方组大鼠给予健脾清化方15 g/(kg·d)灌胃,模型组大鼠给予相同容量的生理盐水灌胃,对照组大鼠不处理。各组干预时间为4周。于治疗前后每周检测大鼠空腹血糖(FBG)及给药4周后血脂水平;应用Affymetrix基因芯片技术检测各组大鼠肝脏组织的差异表达基因;通过基因芯片信号通路找出与健脾清化方影响2型糖尿病大鼠肝脏转录水平表达调控相关的信号通路和基因。结果健脾清化方组治疗后1、2、3、4周FBG水平较本组治疗前明显降低,并低于同时间点模型组(P<0.05);健脾清化方组大鼠血脂水平均较模型组下降(P<0.05或P<0.01)。健脾清化方能显著影响多个如胰岛素分泌通路、脂肪酸代谢通路和TNF信号通路等信号通路,并能上调通路中PCIF1、INSIG1基因的表达。结论健脾清化方可能通过影响多个信号通路中的基因表达来调控2型糖尿病大鼠肝脏基因转录水平,从而降低血糖水平。

Objective To explore possible functional mechanism of Jianpi Qinghua Recipe treating type 2 diabetes mellitus at gene transcriptional level. Methods Randomly selected 40 from 50 Wistar rats to establish type 2diabetes mellitus model,with the other 10 rats taken as control group. Thirty successful modeling rats were randomly divided into model group and Jianpi Qinghua Recipe group,with 15 rats each. Perfused rats in Jianpi Qinghua Recipe group with Jianpi Qinghua Recipe 15 g /（ kg·d）. Perfused rats in model group with normal saline of the same capacity,conducting nothing on rats of control group. Intervention time of each group was all for 4 weeks. Tested levels of fast blood glucose（ FBG） of rats every week before and after treatment,and blood lipid level 4 weeks after treatment;Adopting Affymetrix gene chip technology to test differential expression gene of liver tissue of rats in each groups;Located signal pathways and gene related to Jianpi Qinghua Recipe affecting expression and regulating of level of transcription of livers of rats suffering from 2-diabetes mellitus,through gene chip signal pathways. Results FBG level of Jianpi Qinghua Recipe group decreased remarkably after treating for 1,2,3,4 weeks,and was lower than that of model group at the same time point（ P〈0. 05）; Blood lipid level of rats in Jianpi Qinghua Recipe group decreased compared with that of model group（ P〈0. 05 or P〈0. 01）. Jianpi Qinghua Recipe can remarkably affect several signal pathways,such as insulin secretion pathway,fatty acid metabolism pathway and TNF signal pathway,and can up-regulate the expression of PCIF1 and INSIG1 gene in the pathways. Conclusion Jianpi Qinghua Recipe may regulate gene transcriptional level of livers of rats suffering from type 2 diabetes mellitus by affecting gene expression of multiple signaling pathways,to increase glucose levels.