疏血通注射液对慢性阻塞性肺疾病急性加重期患者PERK-ATF4-CHOP通路的影响
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摘要
目的观察疏血通注射液联合西医治疗慢性阻塞性肺疾病急性加重期(AECOPD)患者的临床疗效及对未折叠蛋白反应(UPR)中PERK-ATF4-CHOP通路的影响。方法将符合纳入标准的70例AECOPD患者随机分为治疗组和对照组,每组35例。对照组给予吸氧、抗感染、解痉平喘、祛痰、营养支持等常规治疗,治疗组在此基础上予疏血通注射液6 mL静脉滴注,每日1次,2组均治疗14 d。统计2组临床疗效,观察2组治疗前后肺功能[第1秒用力呼气容积(FEV_1)、用力肺活量(FVC)、第1秒用力呼气容积占用力肺活量百分比(FEV_1/FVC)、第1秒用力呼气容积占预计值百分比(FEV_1%)]及动脉血气分析[p(O_2)、p(CO_2)、血液酸碱度(pH)]变化,采用酶联免疫吸附法(ELISA)检测2组治疗前后血清葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶(PERK)、活化转录因子4(ATF4)、C/EBP同源蛋白(CHOP)水平,采用qRT-PCR法检测2组治疗前后外周血GRP78 mRNA、PERK mRNA、ATF4 mRNA、CHOP mRNA表达水平。结果治疗组总有效率为91.43%,明显高于对照组的80.00%(P<0.05);治疗后2组FEV_1、FVC、FEV_1/FVC、FEV_1%、p(O_2)、血pH均有不同程度升高(P均<0.05),p(CO_2)均有不同程度降低(P均<0.05),且治疗组改变更明显(P均<0.05);治疗后2组血清GRP78、PERK、ATF4、CHOP水平和GRP78 mRNA、PERK mRNA、ATF4 mRNA、CHOP mRNA表达水平均有不同程度下降(P均<0.05),且治疗组变化更明显(P均<0.05)。结论疏血通注射液联合常规西医治疗AECOPD患者,可一定程度上纠正患者存在的内质网应激状态,从而改善患者肺功能及血气分析,提高临床治疗效果。
Objective It is to observe the clinical efficacy of Shuxuetong injection combined with western medicine in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) and its influence on the PERK-ATF4-CHOP pathway. Methods Seventy patients with AECOPD who met the inclusion criteria were randomly divided into treatment group and control group, thirty-five cases in each group. The control group was treated with conventional therapy such as oxygen inhalation, anti-infection, antispasmodic, antispasmodic, expectorant, and nutritional support, and the treatment group was given Shuxuetong injection 6 mL by intravenously drip additionally, once daily. The two groups were treated with 14 d. After treatment, clinical efficacy and pulmonary function, including forced expiratory volume in the first second(FEV_1), forced vital capacity(FVC), forced expiratory volume in the first second accounted for the percentage of forced vital capacity(FEV_1/FVC), FEV_1 percent predicted(FEV_1/predicted value), and arterial blood gas analysis, including oxygen partial pressure [p(O_2)], carbon dioxide partial pressure [p(CO_2)], blood pH were compared between the two groups, the changes of serum glucose-regulated protein 78(GRP78), protein kinase R-like ER kinase(PERK), activating transcription factor 4(ATF6), C/EBP homologous protein(CHOP) in patients were detected by enzyme-linked immunosorbent assay(ELISA). The changes of GRP78 mRNA, PERK mRNA, ATF4 mRNA, CHOP mRNA expression in peripheral blood of patients before and after treatment were detected by qRT-PCR. Results The total effective rate of treatment group was 91.43%, higher than 80% in the control group(P<0.05); the levels of FEV_1, FVC, FEV_1/FVC, FEV_1%, p(O_2) and pH were increased while the level of p(CO_2) was decreased in the two groups after treatment, and changes in the treatment group were more obvious(P<0.05). After treatment, the levels of serum GRP78, PERK, ATF4, CHOP and the expression of GRP78 mRNA, PERK mRNA, ATF4 mRNA and CHOP mRNA were decreased, and the decrease in the treatment group were more obvious(P<0.05). Conclusion Shuxuetong injection combined with normal western medicine could correct the disorder of endoplasmic reticulum stress to a certain extent in the treatment of AECOPD patients, so as to reduce the patient's symptoms, improve lung function and arterial blood gas analysis, and improve clinical curative effect.
Objective It is to observe the clinical efficacy of Shuxuetong injection combined with western medicine in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) and its influence on the PERK-ATF4-CHOP pathway. Methods Seventy patients with AECOPD who met the inclusion criteria were randomly divided into treatment group and control group, thirty-five cases in each group. The control group was treated with conventional therapy such as oxygen inhalation, anti-infection, antispasmodic, antispasmodic, expectorant, and nutritional support, and the treatment group was given Shuxuetong injection 6 mL by intravenously drip additionally, once daily. The two groups were treated with 14 d. After treatment, clinical efficacy and pulmonary function, including forced expiratory volume in the first second(FEV_1), forced vital capacity(FVC), forced expiratory volume in the first second accounted for the percentage of forced vital capacity(FEV_1/FVC), FEV_1 percent predicted(FEV_1/predicted value), and arterial blood gas analysis, including oxygen partial pressure [p(O_2)], carbon dioxide partial pressure [p(CO_2)], blood pH were compared between the two groups, the changes of serum glucose-regulated protein 78(GRP78), protein kinase R-like ER kinase(PERK), activating transcription factor 4(ATF6), C/EBP homologous protein(CHOP) in patients were detected by enzyme-linked immunosorbent assay(ELISA). The changes of GRP78 mRNA, PERK mRNA, ATF4 mRNA, CHOP mRNA expression in peripheral blood of patients before and after treatment were detected by qRT-PCR. Results The total effective rate of treatment group was 91.43%, higher than 80% in the control group(P<0.05); the levels of FEV_1, FVC, FEV_1/FVC, FEV_1%, p(O_2) and pH were increased while the level of p(CO_2) was decreased in the two groups after treatment, and changes in the treatment group were more obvious(P<0.05). After treatment, the levels of serum GRP78, PERK, ATF4, CHOP and the expression of GRP78 mRNA, PERK mRNA, ATF4 mRNA and CHOP mRNA were decreased, and the decrease in the treatment group were more obvious(P<0.05). Conclusion Shuxuetong injection combined with normal western medicine could correct the disorder of endoplasmic reticulum stress to a certain extent in the treatment of AECOPD patients, so as to reduce the patient's symptoms, improve lung function and arterial blood gas analysis, and improve clinical curative effect.
引文
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[6] 潘高峰,郜玉峰,叶娇娇,等. 慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化[J]. 实用肝脏病杂志,2015,18(2):136-140
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[10] Chen Y,Gui D,Chen J,et al. Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats[J]. Cell Physiol Biochem,2014,33(6):1975-1987
[11] Scheper W,Hoozemans JJ. The unfolded protein response in neurodegenerative diseases:a neuropathological perspective[J]. Acta Neuropathol,2015,130(3):315-331
[12] 殷运收. 疏血通注射液的药理作用及临床应用新进展[J]. 临床医学工程,2011,18 (3):472-473
[13] 努尔买买提·亚生. 疏血通注射液对急性脑梗死缺血再灌注氧化应激水平的影响[J]. 解放军预防医学杂志,2017,35(10):1193-1196
[2] 王婷婷,杜毓锋,刘学军. 内质网应激在PM2.5诱导大鼠肺泡巨噬细胞凋亡中的作用[J]. 国际呼吸杂志,2017,37(5):354-360
[3] 袁婷,张立,贺志飚,等. AMPK调控内质网应激抵抗COPD大鼠肺泡上皮细胞凋亡的实验研究[J]. 现代生物医学进展,2017,17(23):4401-4405
[4] 慢性阻塞性肺疾病急性加重诊治专家组. 慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2014年修订版)[J]. 国际呼吸杂志,2014,34(1):1-11
[5] 何成诗,黄青松. 中西医结合治疗慢性阻塞性肺病急性加重期48例临床研究[J]. 江苏中医药,2010,42(4):31-32
[6] 潘高峰,郜玉峰,叶娇娇,等. 慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化[J]. 实用肝脏病杂志,2015,18(2):136-140
[7] 杨媛媛,刘辉国. 内质网应激及其与呼吸系统疾病的关系[J/CD]. 中华哮喘杂志:电子版,2013,7(4):56-59
[8] 林帆,陈亚红. 内质网应激在呼吸系统疾病中的生物学效应[J]. 中华医学杂志,2015,95(2):150-152
[9] Zhu G,Lee AS. Role of the unfolded protein response,GRP78 and GRP94 in organ homeostasis[J]. J Cell Physiol,2015,230(7):1413-1420
[10] Chen Y,Gui D,Chen J,et al. Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats[J]. Cell Physiol Biochem,2014,33(6):1975-1987
[11] Scheper W,Hoozemans JJ. The unfolded protein response in neurodegenerative diseases:a neuropathological perspective[J]. Acta Neuropathol,2015,130(3):315-331
[12] 殷运收. 疏血通注射液的药理作用及临床应用新进展[J]. 临床医学工程,2011,18 (3):472-473
[13] 努尔买买提·亚生. 疏血通注射液对急性脑梗死缺血再灌注氧化应激水平的影响[J]. 解放军预防医学杂志,2017,35(10):1193-1196