小青龙汤干预哮喘寒饮蕴肺证气道炎症的机制研究
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篇名: 小青龙汤干预哮喘寒饮蕴肺证气道炎症的机制研究
TITLE: Study on the mechanism of Xiaoqinglong decoction in intervening in airway inflammation of asthma with syndrome of cold retention accumulation in lung
摘要: 目的 基于肺腺癌转移相关转录本1(MALAT1)探讨小青龙汤对哮喘寒饮蕴肺证气道炎症的影响及其潜在的作用机制。方法将40只Wistar大鼠按随机数字表法分为空白组、模型组、地塞米松组(阳性对照,1mg/kg)、小青龙汤组(2.72g/kg),每组10只。建立哮喘寒饮蕴肺证大鼠模型,从造模第2天开始给予相应药物,每天1次,连续21d。观察大鼠肺组织病理变化,检测大鼠肺功能,测定大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)、白细胞介素13(IL-13)水平和肺组织中MALAT1、TNF-α、IL-13、IFN-γ、瞬时受体电位M2型(TRPM2)mRNA表达水平以及TRPM2蛋白表达水平。将20只C57BL/6J野生型小鼠和20只C57BL/6JMALAT1(-/-)小鼠按随机数字表法分为野生模型组、野生小青龙汤组、MALAT1(-/-)模型组、MALAT1(-/-)小青龙汤组,每组10只。建立哮喘寒饮蕴肺证小鼠模型,造模第2天开始给予小青龙汤,每天1次,连续21d。检测小鼠血清中SOD、MDA、IFN-γ、TNF-α、IL-13水平和肺组织中TRPM2mRNA及其蛋白表达水平。结果大鼠实验结果显示,与模型组比较,给药组大鼠气道阻力,功能残气量,血清中IL-13、TNF-α、MDA水平,肺组织中炎症浸润和胶原纤维化程度、IL-13、TNF-α、TRPM2表达量均显著降低(P<0.05或P<0.01);呼气流峰值,呼气中期流速,血清中SOD、IFN-γ水平,肺组织中IFN-γ、MALAT1表达量均显著升高(P<0.05或P<0.01)。小鼠实验结果显示,与野生模型组比较,野生小青龙汤组小鼠血清中IL-13、TNF-α、MDA水平均显著降低(P<0.05或P<0.01),IFN-γ、SOD水平均显著升高(P<0.01);与野生小青龙汤组比较,MALAT1(-/-)小青龙汤组小鼠血清中SOD、IFN-γ水平均显著降低(P<0.01),IL-13、TNF-α、MDA水平均显著升高(P<0.05或P<0.01);肺组织中TRPM2mRNA及其蛋白表达量均显著升高(P<0.05)。结论小青龙汤可通过调控MALAT1的表达,调控氧化应激反应,抑制TRPM2的激活,减少体内促炎因子的释放,从而减轻气道炎症反应。
ABSTRACT: OBJECTIVE To investigate the effects and potential mechanisms of Xiaoqinglong decoction on airway inflammation in asthma with syndrome of cold retention accumulation in lung based on the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). METHODS Forty Wistar rats were randomly divided into blank group, model group, dexamethasone group (positive control, 1 mg/kg), and Xiaoqinglong decoction group (2.72 g/kg), with 10 rats in each group. A rat model of asthma with syndrome of cold retention accumulation in lung was established, and the corresponding drugs were administered once daily starting from the second day of modeling for 21 consecutive days. Lung histopathological changes and lung function were evaluated. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), interferron-γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin-13 (IL-13) in serum were measured, and the mRNA expression levels of MALAT1, TNF- α, IL-13, IFN- γ, and transient receptor potential melastatin 2 (TRPM2) in lung tissue were determined. Twenty C57BL/6J wild-type mice and twenty C57BL/6J MALAT1(-/-)mice were randomly divided into wild-type model group, wild-type Xiaoqinglong decoction group, MALAT1 model group, and MALAT1(-/-) Xiaoqinglong decoction group, with 10 mice in each group. The same asthma model was E-mail:yan_peizheng@163.com established, and Xiaoqinglong decoction was administered once daily for 21 days starting from the second day of modeling. The serum levels of SOD, MDA, IFN-γ, TNF-α and IL-13 were measured, along with the mRNA and protein expression levels of TRPM2 in lung tissue. RESULTS The results of the rat experiment showed that, compared with model group, the airway resistance, functional residual capacity, the serum levels of IL- 13, TNF-α and MDA as well as inflammatory infiltration and collagen fiber deposition in lung tissue, and the expressions of IL- 13, TNF-α and TRPM2 in lung tissue were all significantly decreased in the treatment group (P<0.05 or P<0.01). The peak expiratory flow, forced expiratory flow at 50% of forced vital capacity, the serum levels of SOD and IFN-γ, and the expression levels of IFN-γ and MALAT1 in lung tissue were significantly increased (P<0.05 or P<0.01). The results of the mice experiment demonstrated that, compared with the wild-type model group, serum levels of IL-13, TNF-α and MDA in wild-type xiaoqinglong decoction group were significantly reduced (P<0.05 or P<0.01), while serum IFN-γ levels and SOD activity were significantly increased (P<0.01). Compared with the wild-type Xiaoqinglong decoction group, the MALAT1(-/-) Xiaoqinglong decoction group showed significantly decreased serum IFN-γ levels and SOD activity (P<0.01), along with significantly increased levels of IL-13, TNF-α and MDA (P<0.05 or P<0.01), as well as significantly elevated TRPM2 mRNA and protein expression in lung tissue (P<0.05). CONCLUSIONS Xiaoqinglong decoction may alleviate airway inflammation by regulating the expression of MALAT1, modulating oxidative stress, inhibiting TRPM2 activation, and reducing the release of pro-inflammatory cytokines.
期刊: 2025年第36卷第13期
作者: 王彬;赵明哲;孙羽扬;颜培正
AUTHORS: WANG Bin,ZHAO Mingzhe,SUN Yuyang,YAN Peizheng
关键字: 小青龙汤;气道炎症;氧化应激;哮喘;寒饮蕴肺证;肺腺癌转移相关转录本1;瞬时受体电位M2型
KEYWORDS: Xiaoqinglong decoction; airway inflammation; oxidative stress; asthma; syndrome of cold retention accumulation
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