| Backgrounds: Chronic obstructive pulmonary disease (COPD) is a slowlyprogressive disease characterized by airflow obstruction that is not fullyreversible, and mostly associated with the abnormal inflammatory response ofthe pulmonary parenchyma to noxious particles and gases. It is a global diseasedamaging human being’s health seriously, and its mortality rate and disabilityare increasing year by year. In2002COPD was the fifth leading cause of deathin the world. However, according to the world health organization (WHO)estimates, it may rise to be the third leading cause of dead worldwide in2030,and the mutilation rate will also rise to the fifth. At present, glucocorticoids areeffective anti-inflammatory drugs, which were widely used in clinical.Glucocorticoids have become one of the important drugs in the treatment ofvery severe COPD and play an important role in the COPD treatment. But inclinical, the disease has poor sensitivity for anti-inflammatory drugs whencompared with the bronchial asthma which belongs to chronic airwayinflammatory disease, and the curative effect of patients with COPD toglucocorticoids compared with patients with COPD whose basic disease isasthma is poorer. Long-term glucocorticoid treatment cannot effectively reversethe lung function index, but rather causes a long-term dependence ofglucocorticoids in some patients, eventually it produces the so-called"glucocorticoid resistance" phenomenon, and also increases the side effects ofglucocorticoids. At present, glucocorticoid resistance mechanism is not entirelyclear, but scholars generally believe that the glucocorticoid receptor (GRα andGRβ) have a vital role in glucocorticoid resistance. As a functional receptor, GRα has a transcriptional activation function on target gene, while GRβ isconsidered as an endogenous inhibitory factor of GRα plays a negativeregulatory role, and it is related to glucocorticoids resistance. So the expressionof GRα and GRβ, the ratio of them can be used to predict the effect ofglucocorticoids. By analyzing the expression levels of GRα, GRβ and the ratioof GRβ to GRα within target nuclei in peripheral blood mononuclear cells(PBMCs) from patients with COPD, this study want to look for a potential andeffective detection to predict therapy effects of glucocorticoids in patients withCOPD.Objective: To observe the expression of GRα and GRβ of patients withCOPD during the glucocorticoid treatment, discuss the relationship betweenexpression of glucocorticoid receptors and glucocorticoid efficacy, and try toestablish a lab indication to predict the effectiveness of glucocorticoids beforethe glucocorticoid treatment.Methods: The study subjects are42cases patients with COPD in acuteexacerbation period, which were divided into glucocorticoid treatment group(22cases) and non-glucocorticoid treatment group (20cases);8cases healthypersons as control group. The glucocorticoid treatment group was givenappropriate dose of glucocorticoid treatment and conventional treatment, thenon-glucocorticoid treatment group was given conventional treatment exceptglucocorticoid. The patients were took peripheral venous blood in the morningbefore glucocorticoid treatment and after3or8days’ treatment, the proteins innuclei and cytoplasm were separately extracted from the peripheral bloodmononuclear cells, and the protein expression levels of GRα and GRβ inPBMCs were separately determined by ELISA method.Results：1. The age, gender and disease course of COPD patients have little effecton the protein expression of GRα, the protein expression of GRβ, and the ratio of GRβ to GRα in the nuclei (P>0.05); the protein expression of GRα in theCOPD smoking group was lower than the non-smoking group and the healthycontrol group, the differences were statistically significant (P<0.05); the proteinexpression of GRβ and the ratio of GRβ to GRα in the nuclei have nosignificant differences among the three groups(P>0.05). This suggested that thesmoking COPD patients were more likely to have glucocorticoid tolerance.2. The protein expression levels of GRα and GRβ were not statisticallysignificant differences among the grade Ⅱ group, grade Ⅲ group, grade Ⅳgroup and the healthy control group (P>0.05). The ratio of GRβ to GRα in thenuclei of the grade Ⅳ group was significantly lower than the other three groups,the difference was statistically significant(P<0.05). This suggested that thefractionation of lung function in patients with COPD was not significantlyassociated with the protein expression of GRα and GRβ.3. The protein expression of GRα in the COPD group was significantlylower than in the asthma with COPD group and the healthy control group, thedifference was statistically significant(P<0.05); the protein expression of GRβwas not statistically significant difference among the COPD group, asthma withCOPD group and control group (P>0.05); the ratio of GRβ to GRα in the nucleiof the COPD group and control group were significantly higher than those inthe asthma with COPD group(P<0.05).This suggested that the curative effect ofglucocorticoids on COPD patients compared with the COPD patients whosebasic disease were asthma was poorer, it may be associated with low proteinexpression of GRα in COPD patients.4. The protein expression of GRα in COPD patients with glucocorticoidtreatment after3days was lower than that before treatment, but the differencewas not statistically significant(P>0.05); the protein expression of GRβ and theratio of GRβ to GRα in the nuclei after3days’ glucocorticoid treatment weresignificantly higher than that before treatment, the differences were statistically significant(P<0.05).This suggested that short-term glucocorticoid therapy couldincrease the protein expression of GRβ, further influenced the effect ofglucocorticoids.5. The protein expression of GRα and GRβ in COPD patients withglucocorticoid treatment after8days were both lower than that after3days, thedifferences were significant (P<0.05); the ratio of GRβ to GRα in the nucleiafter8days’ glucocorticoid treatment had no statistical significance comparedwith that after3days(P>0.05). With the extension of the glucocorticoid usingtime, the expression of GRα and GRβ have been further restrained, and theeffects of glucocorticoid have been influenced.6. Before the glucocorticoid treatment: the protein expression of GRα andGRβ, the ratio of GRβ to GRα in the nuclei were all showed no significantdifference in the groups of different doses (P>0.05). After3days’glucocorticoid treatment: the protein expression of GRα and GRβ in low-dosegroup>middle-dose group or large-dose group, the differences were statisticallysignificant(P<0.05); the protein expression of GRα were lower than beforetreatment(P<0.05), and the protein expression of GRβ in the middle orlarge-dose group were higher than before treatment(P<0.05); the ratio of GRβto GRα in the nuclei has no statistical significance in different groups (P>0.05),but they were higher than those before treatment (P<0.05).This suggested thatwith the increasing of glucocorticoid dosage, the expression of GRα and GRβhave been further restrained, and the effects of glucocorticoid have beeninfluenced.Conclusion：1. Smoking perhaps may be one of the risk factors of the poor sensitivityof patients with COPD for glucocorticoids.2. There were some relativity between the poor sensitivity of the patientswith COPD for glucocorticoids and the low expression of GRα, the high expression of GRβ in PBMCs or the ratio of GRβ to GRα in the nuclei.3. In a certain dose range, the increasing of using time or dosage ofglucocorticoids both could make glucocorticoids receptors decreaseprogressively, clinical efficacy and glucocorticoids were not in atime-dependent or dose-dependent manner.4. During the treatment of glucocorticoids, the protein expression of GRα,the protein expression of GRβ in PBMCs and the ratio of GRβ to GRα in thenuclei were all may be as the lab indications for treatment effect ofglucocorticoids and the guidelines for using glucocorticoids. |
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