Objective: To investigate the attenuating effect of Hydroxysafflor yellow A(HSYA) on inflammatory injury in chronic obstructive pulmonary disease(COPD). Methods: Rats were randomly assigned to 7 groups according to body weight including normal control group, HSYA blank group(76.8 mg/kg), COPD group, COPD+HSYA(30, 48, 76.8 mg/kg) groups and COPD+dexamethasone(2 mg/kg), 10 in each group. Passive cigarette smoke and intratracheal instil ation of lipopolysaccharides were used to establish a COPD model in rats. Hematoxylin and eosin staining of lung tissue sections was used, real-time polymerase chain reaction(PCR) was used to assay m RNA levels of some cytokines in lung tissues, the cytokines in bronchoalveolar lavage fluid(BALF) were measured by enzyme-linked immunosorbent assay(ELISA), Western blot analysis was used to determine phosphorylated p38 mitogen-activated protein kinase(MAPK) levels in lung tissues, and nuclear factor-κB(NF-κB) p65 protein levels in lung tissues were detected by immunohistochemistry. Results: Lung alveolar septa destruction, alveolus fusion, inflammatory cel infiltration, and bronchiole exudation were observed. These pathological changes were al eviated in the COPD+HSYA group. The m RNA expression of inflammatory factors were significantly increased in lung tissues from COPD rats(all P<0.01) and were inhibited by HSYA. Levels of inflammatory cytokines in BALF of COPD rats were significantly increased(all P<0.01) which were inhibited by HSYA(all P<0.01, 48, 76.8 mg/kg). The levels of p38 MAPK phosphorylation and p65 in lung tissues of COPD rats were significantly increased(al P<0.01) and were suppressed by HSYA(all P<0.01, 48, 76.8 mg/kg). Conclusions: HSYA could alleviate inflammatory cell infiltration and other pathological changes in the lungs of COPD rats. HSYA could inhibit inflammatory cytokine expression, and increase phosphorylation of p38 MAPK and NF-κB p65 in the lungs of COPD rats. The protective mechanism of HSYA to inhibit COPD inflammation might be by attenuating NF-κB an
JIN MingXUE Chang-jiangWANG YuDONG FangPENG Yuan-yuanZHANG Ya-danZANG Bao-xiaTAN Li
Objective:This study observed attenuating effect of hydroxysafflor yellow A(HSYA),an effective ingredient of aqueous extract of Carthamus tinctorius L,on lipopolysaccharide(LPS)-induced endothelium inflammatory injury.Methods:Eahy926 human endothelium cell(EC) line was used;thiazolyl blue tetrazolium bromide(MTT) test was assayed to observe the viability of EC;Luciferase reporter gene assay was applied to measure nuclear factor- κB(NF- κB) p65 subunit nuclear binding activity in EC;Western blot technology was used to monitor mitogen activated protein kinase(MAPKs) and NF- k B activation.Reverse transcription polymerase chain reaction(RT-PCR) method was applied to observe intercellular cell adhesion molecule-1(ICAM-1) and E-selectin mRNA level;EC surface ICAM-1 expression was measured with flow cytometry and leukocyte adhesion to EC was assayed with Rose Bengal spectrophotometry technology.Results:HSYA protected EC viability against LPS-induced injury(P<0.05).LPS-induced NF-κB p65 subunit DNA binding(P<0.01) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α(I κ Bα) phosphorylation was inhibited by HSYA.HSYA attenuated LPS triggered ICAM-1 and E-selectin mRNA levels elevation and phosphorylation of p38 MAPK or c-Jun N-terminal kinase MAPK.HSYA also inhibited LPS-induced cell surface ICAM-1 protein expression(P<0.01) and leukocyte adhesion to EC(P<0.05).Conclusion:HSYA is effective to protect LPS-induced high expression of endothelium adhesive molecule and inflammatory signal transduction.
