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ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.
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Objective To explore the relationship of stromal derived factor 1α (SDF-1α) and CD44variant isoforms (CD44v6) with progress of multiple myeloma (MM). Methods Bone marrow mononuclear cells(MNCs) and bone marrow stromal cells (BMSCs) from 24 cases of MM patients (14 cases of untreated and relapsed and 10 cases of stable MM patients) and 15 cases of subjects were investigated as potential SDF-1αand CD44v6 product. The level of SDF-1α and CD44v6 of the conditioned media from MM patients and subjects were analyzed by ELISA. Results The level of SDF-1α and CD44v6 from MNCs in untreated and relapsed MM patients [(7232.41 ± 2644.97) pg/ml and (34.34 ± 13.20) ng/ml] were significantly higher than stable MM patients [(2315.49 ± 748.29) pg/ml and (15.69 ± 5.28) ng/ml] (t =6.25, t= 7.82, P ＜0.05) and 15 subjects [(1149.52 ± 636.06) pg/ml and (4.85 ± 3.62) ng/ml] (t= 4.60, t = 7.61, P＜ 0.05). The level of SDF-1α in stable MM patients was different from healthy subjects (P ＜0.05), but the level of CD44v6 in stable MM patients was not different from controls. The level of SDF-1α and CD44v6 in stable MM patients were significantly higher than health subjects (t = 2.99, t= 4.87, P ＜0.05). The level of SDF-1α was also detected from BMSCs of MM patients. When human MM cell lines U266 were adhered to BMSCs of 9 untreated and relapsed MM patients,and added rhIL-6 to it, there was significant increase of SDF-1α, compared with BMSCs in subjects and MM patients. The expression level of SDF-lα was correlated with the level of CD44v6 (r =0.51, P =0.03). Conclusion The increase of SDF-1α (may be produced by myeloma cells and BMSCs) and CD44v6 (may be produced by myeloma cells) activity is associated with the progress or pathogenesis of MM, and may be involved with tumor invasion. The completion of these processes in vivo may need participation of myeloma cells, BMSCs, IL-6,SDF-lα and CD44v6.
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he activity of MMP-2 and MMP-9 via ERK1/2 signaling pathway.