汉黄芩素对慢性阻塞性肺疾病模型大鼠气道炎症的影响及机制-中国药房

汉黄芩素对慢性阻塞性肺疾病模型大鼠气道炎症的影响及机制

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篇名：	汉黄芩素对慢性阻塞性肺疾病模型大鼠气道炎症的影响及机制
TITLE：	Effects and mechanisms of wogonin on airway inflammation in rats with chronic obstructive pulmonary disease
摘要：	目的研究汉黄芩素（Wog）对慢性阻塞性肺疾病（COPD）模型大鼠气道炎症的影响及可能机制。方法将84只大鼠按随机数字表法分为对照组，模型组，Wog低、高剂量组（灌胃给药，50、100mg/kg），氨茶碱组（阳性对照，灌胃给药，2.3mg/kg），重组大鼠受体相互作用蛋白激酶1[rRIPK1，受体相互作用蛋白激酶1（RIPK1）激活剂]组（尾静脉注射给药，8µg/kg），Wog高剂量+rRIPK1组（灌胃100mg/kgWog并尾静脉注射8µg/kgrRIPK1），每组12只。除对照组外，其余各组大鼠均利用烟熏联合气管注射脂多糖的方法构建COPD模型。建模24h后，进行给药处理；每天给药1次，持续4周。末次给药后，测定各组大鼠的吸气峰流量（PIF）、呼气峰流量（PEF）、每分钟通气量（MV）和第1秒用力呼气容积（FEV1）/用力肺活量（FVC）比值，测定大鼠血清中白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）水平，观察大鼠肺组织病理形态学变化，测定大鼠肺上皮细胞凋亡率，并测定大鼠肺组织中RIPK1、RIPK3、混合系激酶区域样蛋白（MLKL）mRNA和RIPK1、RIPK3、磷酸化MLKL（p-MLKL）蛋白表达水平。结果与对照组比较，模型组大鼠PIF、PEF、MV、FEV1/FVC比值显著降低（P＜0.05），IL-1β、IL-6、TNF-α水平显著升高（P＜0.05），肺组织有大量炎症细胞浸润、支气管壁增厚，肺上皮细胞凋亡率及RIPK1、RIPK3、MLKLmRNA和RIPK1、RIPK3、p-MLKL蛋白表达水平也显著升高（P＜0.05）。与模型组比较，Wog低、高剂量组大鼠上述指标均显著改善（P＜0.05），病理损伤明显减轻；而rRIPK1组大鼠对应指标却显著恶化（P＜0.05），病理损伤也进一步加重；并且，rRIPK1可明显减弱高剂量Wog对COPD大鼠气道炎症和RIPK1/RIPK3/MLKL通路的抑制作用（P＜0.05）。结论Wog可能通过抑制RIPK1/RIPK3/MLKL信号通路改善COPD大鼠的气道炎症。
ABSTRACT：	OBJECTIVE To study the effects and potential mechanism of wogonin （Wog） on airway inflammation in rats with chronic obstructive pulmonary disease （COPD）. METHODS Eighty-four rats were randomly divided into control group， model group， Wog low-dose and high-dose groups （intragastric administration of 50， 100 mg/kg）， aminophylline group （positive control， intragastric administration of 2.3 mg/kg）， recombinant rat receptor-interacting protein kinase 1 [rRIPK1， receptor-interacting protein kinase 1 （RIPK1） activator] group （tail vein injection of 8 µg/kg）， and Wog high-dose+rRIPK1 group （intragastric administration of Wog 100 mg/kg+tail vein injection of rRIPK 8 µg/kg）， with 12 rats in each group. Except for control group， COPD model of other groups was induced by smoking combined with tracheal injection of lipopolysaccharide. Twenty-four hours after successful modeling， the rats were administered once a day for 4 weeks. The changes of peak inspiratory flow （PIF）， peak expiratory flow （PEF） and minute ventilation （MV），forced expiratory volume in one second（FEV1）/forced vital capacity（FVC） were measured after the last medication； the serum levels of interleukin 1β（IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） were measured by ELISA； the pathological changes of lung tissue in rats were observed； the apoptotic rate of pulmonary epithelial cells was detected. mRNA expressions of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL）， and protein expressions of RIPK1， RIPK3 and p-MLKL were all detected in lung tissue of rats. RESULTS Compared with control group， PIF， PEF， MV and FEV1/FVC of model group were decreased significantly （P＜0.05）， while the levels of IL-1β， IL-6 and TNF- α were increased significantly （P＜0.05）； there was a large number of inflammatory cells infiltration in the lung tissue and bronchialwall thickening in model group； the apoptotic rate of pulmonary epithelial cells，mRNA expressions of RIPK1， RIPK3 and MLKL， protein expressions of RIPK1， RIPK3 and p-MLKL were increased significantly （P＜0.05）. Compared with model group， above indexes of rats were improved significantly in Wog low-dose and high-dose groups （P＜0.05）， and pathological injuries were alleviated significantly. The corresponding indexes of rats were worsened in rRIPK1 group （P＜0.05）， and pathological damage had further worsened. rRIPK1 significantly attenuated the inhibitory effect of high-dose Wog on airway inflammation and RIPK1/RIPK3/ MLKL pathway in COPD rats （P＜0.05）. CONCLUSIONS Wog may improve airway inflammation in COPD rats by inhibiting RIPK1/RIPK3/MLKL signal pathway.
期刊：	2023年第34卷第09期
作者：	邹曲；符丹丹；范腾阳；欧阳瑶
AUTHORS：	ZOU Qu，FU Dandan，FAN Tengyang，OUYANG Yao
关键字：	汉黄芩素；慢性阻塞性肺疾病；气道炎症；受体相互作用蛋白激酶1；受体相互作用蛋白激酶3；混合系激酶区域样蛋白
KEYWORDS：	wogonin； chronic obstructive pulmonary disease； airway inflammation； receptor-interacting protein kinase 1；
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