ABSTRACT
Objective:Dipeptidyl peptidase I(DPPI),a lysosomal cysteine protease for serine proteases activation,highly expressed in granule immune cells.This study used collagen induced arthritis(CIA) rat model to investigate the effects of Triperygium Wilfordii Polyglucoside(TWP) on DPPI activity and the pharmacological mechanism in RA treatment.Methods:Rats were divided into four groups randomly,the blank control group,the CIA model group,the high dose (5.0 mg/100 g body-weight) and low dose(2.5 mg/100 g body-weight)treatment group.Bovine collagen-Ⅱ plus complete Freund′s adjuvant injected twice in rats.Physical assessments were carried out.12 days post-injections,the rats of treatment group were intragastric administered with TWP every day.The rats were killed after two week administrations.Serum and synovial membrane homogenates were collected and DPPI activity was detected by fluorescence substrate.Joint HE staining and cell counting were carried out,Zymography was used to detect the MMP-2/9 activity in synovial fluids.Total protein in synovial membrane homogenates were measured by BCA method.Results:TWP could reduce the number of CIA synovial tissue mast cells,inhibited DPPI activity in the synovial fluids and in serum.The expression levels of MMP-2/9 activity and synovium total protein content were also reduced by TWP.Conclusion:Triperygium Wilfordii Polyglucoside has inhibitory effects on DPPI activity on CIA rats,which might be the one of the pharmacological mechanisms in RA treatment.
ABSTRACT
Objective To investigate the clinical effect of budesonide/formoterol single inhaler combined with tiotropium bromide in stable chronic obstructive pulmonary disease (COPD).Methods 80 cases of patients with stable COPD in China Aviation Industrial Xi'an Hospital from May 2014 to May 2016 were divided into observation group and control group,40 cases in each group.Patients in the control group were treated with budesonide/formoterol single inhaler,and in the observation group were treated with budesonide/formoterol single inhaler combined with tiotropium bromide.Compared the pulmonary function,life quality,serum levels of matrix metalloproteinases 9 (MMP-9) and interleukin 6 (IL-6),drug adverse reaction during the treatment and exacerbations episodes within the next six months.Results After treatment,the FEV1,FEV1/FVC,FEV1％ of two groups were significantly higher than before treatment (P ＜ 0.05),and in the observation group were significantly higher than that in control group (P ＜ 0.05).SGRQ scores,serum levels of MMP-9 and IL-6 of two groups were significantly lower than before treatment (P ＜ 0.05),and these indexes in the observation group were significantly lower than that in control group (P ＜ 0.05).The differences in the adverse reaction rate of two groups has no significant,the number of acute exacerbation in observation group were significantly lower than that of control group (P ＜ 0.05).Conclusion Budesonide/formoterol single inhaler combined with tiotropium bromide has remarkable clinical effect in stable COPD,and can effectively improve the pulmonary function,life quality,reduce the number of acute exacerbation,and reduce the serum levels of MMP-9,IL-6.
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Objective To study the relationship of the plasma levels of miRNA-491-5p in Han population in Shaanxi Province and the changes of single nucleotide polymorphisms (SNP ) of the target gene matrix metalloproteinases-9 (MMP-9 ) of miRNA-4 9 1-5 p (has-miR-4 9 1-5 p ) with the incidence risk and prognosis of premature coronary artery disease (pCAD)through the case-control design.Methods In this study,we made a consecutive recruitment of 270 pCAD cases in the case group and 300 cases in the control group.Using the polymorphism method of polymerase chain reaction and restriction fragment length (PCR-RFLP),target gene MMP-9 of has-miR-491-5p and rs1056628 genotypes was detected to compare the association between the variant genotypes and pCAD.Results In the changes of rs1056628C-A polymorphisms,compared with that of CC genotypes (the incidence was 42%),the risks of having coronary heart disease in the individuals carrying CA and AA genotypes were 31%,the difference was statistically significant (P=0.045).The risks of developing coronary heart disease in the individuals carrying CA and AA genotypes were reduced more significantly in the population with low total cholesterol (TC),and low low-density lipoprotein cholesterol (LDL-C).Conclusion Target gene MMP-9 of has-miRNA-491-5p rs1056628C-A polymorphism is associated with the reduced incidence risk of pCAD,and carrying C alleles is an independent risk factor for pCAD.
ABSTRACT
Objective To explore molecular mechanism of expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells induced by all-trans refinoic acid (ATRA). Methods MTr method was used to detect the proliferation of HL-60 cells induced by ATRA,cell cycle and CD11b expression in HL-60 cells were detected by flow cytometry. Expression of VEGF, c-myc, by-poxia-inducible factor(HIF)-lα, matrix metalloproteinase (MMP)-9 and MMP-2 mRNA were detected by semi-quantitative RT-PCR. VEGF protein in HL-60 cells culture supernatant was measured by ELISA before and after being induced by ATRA. Results After treatment with ATRA,the proliferation of HL-60 cells was obviously inhibited, CD11b expression increased, trend of granulocyte directional differentiation emerged, and differentiation degree was increasd(P <0. 05) ;expression level of c-my and VEGF mRNA was down-regulated (P < 0. 05), but expression level of HIF-1α mRNA was up-regulated (P < 0. 05). VEGF protein level in HL-60 cells culture supernatant was decreased by blocking the expression of MMP-9 or MMP-2(P <0. 05).Conclusion VEGF expression has positive correlation with c-myc expression,but has negative correlation with HIF-1α expression. MMP-9 and MMP-2 may be the main factors regulating VEGF secretion in HL-60 cells.