ABSTRACT
Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method, and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.
ABSTRACT
Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup(10 g·kg-1),and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8,CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.
ABSTRACT
Objective:To observe the clinical efficacy of modified Erchentang on CXC chemokine ligand receptors (CXCR1/2)and their ligands CXCL8,macrophage inflammatory protein -2(MIP-2) in patients of chronic obstructive pulmonary disease(AECOPD)at acute exacerbation stage,and assess the effect and mechanism of modified Erchentang on anti-inflammatory in patients of AECOPD. Method:This study was a multicenter, randomized single blind, controlled trial. The authors selected 200 cases in conformity to the standards of AECOPD. The AECOPD patients were randomly divided into modified Erchentang group and control group. In addition to the western medicine, modified Erchentang was also given to the modified Erchentang group, and Jizhitangjiang was given to the control group for 14 days. Each group was observed for the alleviation of the symptoms. Euzyme-linked immunosorbent assay (ELISA) was used to determine the levels of CXCL8 and MIP-2 in the patients' plasma of all groups before and after treatment. Western blot were used to detect the levels of CXCR1, CXCR2 and CXCL8 protein in peripheral blood mononuclear cells(PBMCs). Immunocytochemistry (ICC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in PBMCs. Result:The level of CXCL8 in plasma, and the expressions of CXCR1, CXCR2 and CXCL8 mRNA and protein in the modified Erchentang group were decreased significantly than those in the control group(PPConclusion:Modified Erchentang has an anti-inflammatory effect on AECOPD. Its mechanism may be related to the down-regulation of the expressions of CXCL8, CXCR1 and CXCR2, the reduction of synthesis and release of CXCL8 and MIP-2, the inhibition of the chemotaxis and activity of inflammatory cells, and the prevention of inflammation progress.
ABSTRACT
Objective: To observe the effect of modified Erchentang on the expressions of NLRP3 inflammasome genes in peripheral blood mononuclear cells (PBMCs) and the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)and chemokine8 (CXCL8) in lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the molecular mechanism of modified Erchentang against inflammation of COPD. Method: Forty SD rats were randomly divided into normal control group, model group, MCC950 (NLRP3 inhibitor) group and modified Erchentang group. The COPD model of rats was prepared by using cigarette smoke and dripping with lipopolysaccharide (LPS). During the modeling period (from the 1st to the 30th day), the MCC950 group received a single intraperitoneal injection with 60 mg · kg-1 on the first day of the experiment,and the modified Erchentang group was given intragastric administration with 10 g · kg-1, once every 2 days. From the 31st to the 45th day, the MCC950 group was intraperitoneally injected with 3 mg · kg-1, once every 2 days, the modified Erchentang group was given intragastric administration with 10 g · kg-1, twice a day, and the normal group and the model group received normal saline (NS) with 10 g · kg-1, twice a day. The levels of interleukin-1β(IL-1β), interleukin-18(IL-18) and chemokine8 (CXCL8) in rats lung tissue homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteinyl aspartate specific proteinase-1 (Caspase-1) mRNA in PBMCs were measured by Real-time fluorescence quantitative PCR (Real-time PCR). Western blot was used to detect the levels of NLRP3, ASC and Caspase-1 proteins in PBMCs. Immunohistochemical(IHC)method was used to detect the expressions of NLRP3, ASC and Caspase-1 proteins in lung tissues. Result: The expressions of NLRP3, ASC and Caspase-1 mRNA and protein were increased significantly (PPPβ and CXCL8 in lung tissue homogenate in model group were significantly higher than those in the control group. However, compared with model group, the levels of IL-18, IL-1β and CXCL8 were decreased significantly (PPConclusion: NLRP3 inflammasome is involved in the inflammatory response in COPD rats. Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be correlated with the reduction of NLRP3, ASC and Caspase-1 gene expressions, and the inhibition of the release of IL-18, IL-1β and CXCL8.
ABSTRACT
Objective: To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB (NF-κB) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD). Method: Forty SD rats were randomly divided into normal group, model group, modified Erchentang group and EVP4593 (NF-κB inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling, normal and model groups were intragastrically given normal saline solution, EVP4593 group was given EVP4593(1 mg · kg-1) through subcutaneous injection, and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g · kg-1) for 14 days. The levels of high mobility group box 1(HMGB1), chemokines CXCL-2, CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB p65 (NF-κB p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4, MyD88, NF-κB p65 and p-NF-κB p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4, MyD88 and p-NF-κB p65 protein in the lung tissue. Result: The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 were increased significantly (PPκB p65 mRNA and protein were decreased significantly (PConclusion: Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-κB pathway and the reduction of the release of HMGB1, CXCL-2, CXCL-3 and MCP-1.