ABSTRACT
OBJECTIVE：To predict the pot ential target and mechanism of Xintong Changluo Method carrier-Compund Shensu Ⅱ couplet medicine of Bupleurum falcatum-Scutellaria baicalensis intervening in podocyte lesion ，and to provide reference for the development of sequential clinical and basic research of Xintong Changluo Method in the prevention and treatment of podocyte lesion. METHODS ：Based on TCMSP database ，chemical components and target protein of B. falcatum and S. baicalensis were retrieved，and Cytoscape 3.2.1 software was used to draw a “TCM-component-target”network. The targets related to podocyte lesion were searched from OMIM database ，DrugBank database and Digsee online text ，and the intersection genes of above targets and“B. falcatum -S. baicalensis ”target were obtained by Venny 2.1.0 online mapping tool. The protein-protein interaction （PPI） network was constructed by STRING database ，and the core targets were obtained by topology analysis of the network by using CytoNCA plug-in Cytospace 3.2.1 software. With the help of DAVID database ，the fu nction of Gene Ontology （GO）was annotated and KEGG pathway was enriched ；and the enrichment results were visualized through OmicShare Tools online mapping platform. RESULTS ：Based on retrieval results of TCMSP database，44 active components were obtained ，involving 13 com of B. falcatum and 32 of S. baicalensis ； stigmasterol is common component of B. falcatum and S. baicalensis Quercetin，kaempferol and wogonin were the compounds withmain potential targets. T he target proteins wi th high node degree were prostaglandin endoperoxide synthase 2（PTGS2），PTGS1， nuclear receptor coactivator 2 and heat shock protein 90α，which were associated with 37，30，25 and 25 active components respectively. Twenty genes were obtained from the interaction between “B. falcatum -S. baicalensis ”and podocyte lesion related targets，including PTGS2，VEGFA，MMP9，TNF and IL6. PPI network diagram of the above intersection genes contained 20 nodes and 110 lines，with MMP9，VEGFA，IL6 and other genes at the core. The results of GO analysis showed that a total of 154 biological information items were obtained （P＜0.05），including 139 biological process items ，8 cell composition items and 7 molecular function items. Among them ，biological processes mainly involved in the positive regulation of NO biosynthesis process ， inflammatory response ，immune response. Cell composition mainly involved in extracellular space ，extracellular region ，external side of plasma membrane ，etc.，and molecular function mainly involved in protein binding ，cytokine activity ，growth factor activity，etc. At the same time ，47 KEGG pathways were obtained （P＜0.05），mainly including cytokine-cytokine receptor interaction，rheumatoid arthritis ，malaria，cancer signaling pathways. CONCLUSIONS ：The active components of Compund Shensu Ⅱ couplet medicine of “B. falcatum -S. baicalensis ”may act on MMP9，VEGFA，IL6，TNF and other targets through cytokine-cytokine receptor interaction ，rheumatoid arthritis ，malaria，cancer signal pathway ，so as to play its intervention effect on podocyte lesion.
ABSTRACT
Objective To observe and discuss the effect of the traditional Chinese drug complex prescription ShensuⅡfrom Xintong Changluo therapeutic principle on renal interstitial fibrosis (RIF) and transforming growth factor-β1 (TGF-β1) expresssion in focal segmental glomerulosclerosis (FSGS) model rats. Methods Forty-eight healthy male SD rats were randomly divided into control group (n=12) and modeling group (n=36). Rats of modeling group were injected by doxorubicin hydrochoride for FSGS model. Rats of modeling group were sub-divided into model group, benazepril group and TCM group randomly. In 12 weeks, TCM group was given by intragastric administration of ShensuⅡ(3.5 g/100 g), benazepril group was given by intragastric administration of benazepril suspension (0.33 mg/100 g), control group and model group were given by intragastric administration of same volume of saline. HE/Masson staining was used to observe changes of tubulointerstitial pathomorphology. The degree of injury and fibrosis was measured. The expressions of fibronectin (FN) and TGF-β1 were detected by immunohistochemical SP method. Results The process of renal interstitial fibrosis was slower in FSGS rats of TCM group. Renal interstitial pathological index was 1.51 ± 0.80 in TCM group, which was lower than that of model group (2.18 ± 0.38) and benazepril group (1.79 ± 0.24). The index of renal interstitial fibrosis was 2.39 ± 0.13 in TCM group, which was lower than that of model group (3.11 ± 0.25) and benazepril group (2.80 ± 0.41). The relative expression of FN in renal interstitial was 14.19 ± 3.06 in TCM group, which was lower than that of model group (21.25 ± 3.31) and benazepril group (18.51±2.29). The relative expression of TGF-β1 in renal interstitial was 2.64±0.21 in TCM group, which was lower than that of model group (6.02 ± 0.12) and benazepril group (3.79 ± 0.46). All the differences were statistically significant (P<0.05). Conclusion Xintong Changluo complex prescription ShensuⅡcan reduce the process of renal interstitial fibrosis in FSGS model rats, which may be related with the inhibiting expression of TGF-β1.