Analysis of Yishen Sanjie compound for inhibiting adriamycin nephropathy based on RNA-seq technique mechanism of glomerulosclerosis
Objective:To analyze the mechanism of Yishensanjie compound in inhibiting glomerulosclerosis of adriamycin ne-phropathy based on transcriptome sequencing(RNA-seq).Method:Forty SD rats were randomly divided into 4groups,which were normal group,adriamycin model group,benazepril hydrochloride control group and Yishensanjie compound group(hereinafter re-ferred to as normal group,model group,control group and compound group),and adriamycin hydrochloride was injected into the tail vein twice to prepare adriamycin rat nephropathy model.The control group and compound group were given 10mg/kg/d benazepril hydrochloride and 6.24g/kg/d Yishensanjie compound decoction for 6weeks,and the other groups were given the same dose of nor-mal saline.The general situation,24h urinary protein quantity(24h UTP),blood urea nitrogen(BUN)and blood creatinine(SCr)indexes of the rats were compared before and after gavage.The pathological changes of kidney were observed under electron microscope.At the same time,the revived HBZY-1rat mesangial cells were divided into the above 4groups,and the apoptosis model of rat renal mesangial cells was induced by doxorubicin at 40μM concentration,and the cells of each group were treated correspond-ingly,and the apoptosis of rat mesangial cells was observed.On this basis,the normal group,model group and compound group cells were sequenced by RNA,screened for differentially expressed genes(DEG),and the common DEG was enriched by gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).Results:The animal experimental study showed that Yishenanjie compound could improve the mental states of lax stoses,dull reaction and decreased activity in rats with doxorubicin nephropathy,re-duce the levels of UTP,BUN and SCr for 24h(P＜0.05),reduce the matrix deposition in mesangial region of the glomerulus in rats with doxorubicin nephropathy,improve the condition of basement membrane ischemia and crease,and inhibit the degree of glomeru-lar sclerosis.The cell experiment showed that Yishensanjie compound could delay the apoptosis of HBZY-1rat mesangial cells in-duced by doxorubicin and inhibit glomerular sclerosis.According to the results of RNA-seq,there were 863common DEGs of Yishen-sanjie compound against doxorubicin nephropathy glomerulosclerosis,542of which were up-regulated and 321of which were down-regulated.GO analysis showed that these DEGs were mainly enriched in three aspects:biological processes,cell components and mo-lecular functions.Among them,GO functions related to glomerulosclerosis include positive regulation of cell migration,cell adhe-sion,extracellular matrix,integrin binding,CXCR chemokine receptor binding,chemokine activity,etc.KEGG analysis showed that the above DEG was enriched in 19pathways(P＜0.05),among which extracellular matrix(ECM)-receptor interaction,nuclear transcription factor κB(NF-κB)signaling pathway and calcium signaling pathway were closely related to glomerulosclerosis.Con-clusion:Yishensanjie compound can inhibit the process of glomerulosclerosis in doxorubicin nephropathy by inhibiting the apoptosis of mesangial cells and reducing the deposition of mesangial matrix.Its effect may be through positively regulating the migration of me-sangial cells,participating in the mitotic cell cycle,promoting cell adhesion and other biological processes,and acting on the extra-cellular matrix.It plays the molecular functions of integrin binding,CXCR chemokine receptor binding and promoting chemokine ac-tivity,which is closely related to the regulation of ECM-receptor interaction,NF-κB signaling pathway and calcium signaling path-way.
万方数据
维普
