OBJECTIVETo investigate the expression of mdr1 gene in hematopoietic cells of a murine bone marrow transplantation model and to explore the feasibility of transferring mdr1 gene into hematopoietic cells to pro-vent myelosuppression from chemotherapy.

METHODSmdr1 gene was transferred into hematopoietic cells of murine bone marrow by retrovirus vector. The expression and function of mdr1 gene in vivo was tested in a murine bone marrow transplantation model.

RESULTS(1) mdr1 gene was successfully transferred into murine MNC, the transduction rate was 35%. (2) mdr1 gene transferred murine bone marrow transplantation model was established successfully by scheduled-bone marrow transplantation method. (3) In 1 approximately 5 months period, stable and effective expression of mdr1 gene could be detected in hematopoietic cells of the recipient mouse, the percentage of mdr1 gene expression cells in recipient's hematopoietic cells decreased monthly to 8.0%, 8.0%, 7.5%, 4.0% and 3.0%. (4) mdr1 expression hematopoietic cells had efficient resistance to chemotherapy.

CONCLUSIONIt is an effective approach to transfer mdr1 gene into hematopoietic cells for preventing myelosuppression in chemotherapy.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Bone Marrow Transplantation ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; Gene Expression ; Genetic Vectors ; genetics ; Hematopoietic Stem Cells ; cytology ; drug effects ; metabolism ; Leukocyte Count ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Paclitaxel ; pharmacology ; Retroviridae ; genetics ; Transfection

Objective To investigate the mechanism of Sini San Formula in the treatment of ulcerative colitis and depression through"homotherapy for heteropathy"based on network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the potential active components and their related targets;GeneCards,CTD,and TTD databases were used to screen the disease-related targets of ulcerative colitis and depression;the intersection of the predicted targets of the active components and the disease-related targets was used to obtain the potential targets(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,and Cytoscape 3.7.2 software to construct a"Chinese medicinals-active components-diseases-common targets"network to analyze the core components;importing the common targets into the STRING database,constructing a common protein-protein interaction(PPI)network.The GO function and KEGG pathway enrichment of the shared targets were analyzed by DAVID database,and molecular docking between the core components and the key targets was verified.Results A total of 136 active components of Sini San Formula were obtained,and 220 potential targets of action(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,involving 657 biological processes,70 cellular components,147 molecular functions and 133 signaling pathways.The screening yielded core active compounds such as quercetin,kaempferol,lignans,naringenin,7-methoxy-2-methylisoflavone,key target proteins such as JUN,MAPK3,STAT3,AKT1,and MAPK1,as well as signaling pathways such as TNF,IL-17,Th17 cellular differentiation,HIF-1,and Toll-like receptor.Five potential key targets have strong binding activity to quercetin,kaempferol,lignans and naringenin.Conclusion Sini San Formula may act on key targets such as JUN,MAPK3,STAT3,AKT1,MAPK1,etc.through active components such as quercetin,kaempferol,lignocerotonin,naringenin,etc.,and play the role of"homotherapy for heteropathy"for ulcerative colitis and depression through the signaling pathways such as TNF,IL-17,HIF-1,Toll-like receptor and Th17 cell differentiation.