ABSTRACT
ObjectiveTo observe the influence of Bupi Yishen decoction on the curative effect of diabetic kidney disease rats and the tubuloglomerular feedback. MethodAmong the 100 SD male rats， 25 were randomly selected as the normal group， and the remaining 75 were treated with high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin （STZ） to establish diabetic rat model. The model rats were randomly divided into model group， Bupi Yishen group and losartan group. Bupi Yishen group and Losartan group were given Bupi Yishen decoction （23.4 g·kg-1） and losartan tablet （9 mg·kg-1）， respectively by gavage， and normal group and model group received equal volume of distilled water via intragastric administration. The treatment lasted for 11 consecutive weeks. Random blood glucose was measured once every two weeks. Rats in each group were put into metabolic cage and 24-hour urine volume was recorded. At the end of week 11， the rats were sacrificed for index detection. Enzyme linked immunosorbent assay （ELISA） was used to determine the quantification of 24-hour urinary microalbumin excretion rate （24 h UAER）， renal tubular injury-related proteins and urine creatinine. Blood was collected for creatinine and urea nitrogen detection. Hematoxylin-eosin （HE） staining， periodic acid-schiff （PAS） staining and Masson staining were performed to observe the pathological changes of the kidney of rats. The expression of sodium-glucose cotransporter 1 （SGLT1）， sodium-glucose cotransporter 2 （SGLT2）， sodium-potassium-chloride cotransporter 2 （NKCC2） and connexin 40 （CX40） was detected by immunohistochemistry. The location of adenosine type Ⅰ receptor （A1AR） in kidney was observed by immunofluorescence. In addition， the expression of SGLT1， SGLT2， NKCC2， CX40 and A1AR in renal tissues was determined by Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， renal pathology in model group showed increased glomerular volume， thickened basement membrane， and shed renal tubule epithelial cells. Compared with the model group， the renal pathology of bupiyishen group was improved. Compared with normal group， random blood glucose at different time points， 24 h UAER and renal tubule-injury-related proteins were increased in model group （P<0.01）， and the expressions of SGLT1 and SGLT2 in renal tissue were increased （P<0.01）， and the expression of NKCC2， CX40 and A1AR decreased （P<0.01）. Compared with the model group， the random blood glucose， 24 h UAER and renal tubular injury-related proteins in Bupi Yishen group decreased （P<0.01）， the expressions of SGLT1 and SGLT2 were down-regulated， and the expressions of NKCC2， CX40 and A1AR were increased （P<0.05）. ConclusionBupi Yishen decoction can improve glomerular and renal tubular injury and alleviate early hyperfiltration in diabetic kidney disease rats. The intervention effect of Bupi Yishen decoction on diabetic kidney disease is related to the regulation of tubuloglomerular feedback.
ABSTRACT
OBJECTIVE@#To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula.@*METHODS@#All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data.@*RESULTS@#The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions.@*CONCLUSIONS@#QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.