黄芩苷通过调节miR⁃223⁃3p/NLRP3通路对脓毒症急性肺损伤大鼠的保护作用  

Benefits of baicalin via miR⁃223⁃3p/NLRP3 pathway modulation on rats with sepsis⁃induced acute lung injury

作　　者：李长力[1] 郑喜胜[1] 贾明雅[1] LI Chang-li;ZHENG Xi-sheng;JIA Ming-ya(Department of Critical Care Medicine,Henan Nanyang Central Hospital,Nanyang 473000,China)

机构地区：[1]河南省南阳市中心医院重症医学科,河南南阳473000

出　　处：《中成药》2021年第8期2047-2052,共6页Chinese Traditional Patent Medicine

摘　　要：目的研究黄芩苷调节miR⁃223⁃3p/NOD样受体蛋白3(NLRP3)通路对脓毒症急性肺损伤(ALI)大鼠的保护作用。方法构建脓毒症ALI大鼠模型,实验分为假手术组、模型组、地塞米松组、低剂量黄芩苷组、中剂量黄芩苷组、高剂量黄芩苷组。酶联免疫吸附法(ELISA)测定各组大鼠血清TNF⁃α(肿瘤坏死因子⁃α)、IL⁃1β(白细胞介素1β)、IL⁃10水平;苏木素⁃伊红(HE)染色观察肺组织病理学变化;测定大鼠肺组织含水量及肺泡液体清除率(AFC);实时荧光定量PCR(RT⁃qPCR)测定各组大鼠肺组织miR⁃223⁃3p水平;蛋白印迹法测定各组大鼠肺组织NLRP3水平。结果与假手术组比较,模型组大鼠血清IL⁃1β、TNF⁃α水平和WW/DW比值、肺组织NLRP3水平升高(P<0.05),血清IL⁃10水平和AFC值、肺组织miR⁃223⁃3p水平降低(P<0.05);同时模型组大鼠肺泡完整性破坏,肺泡萎陷,肺间质明显水肿,大量炎症细胞浸润,肺组织病理得分升高(P<0.05)。经黄芩苷治疗后,随着给药剂量增高,血清IL⁃1β、TNF⁃α水平和WW/DW比值、肺组织NLRP3水平降低(P<0.05),血清IL⁃10水平和AFC值、肺组织miR⁃223⁃3p水平升高(P<0.05),呈剂量依赖性;同时大鼠肺泡结构恢复,肺间质水肿缓解,炎症细胞浸润减少,肺组织病理评分降低(P<0.05),且呈剂量依赖性。结论黄芩苷可通过下调促炎因子IL⁃1β、TNF⁃α水平,上调抑炎因子IL⁃10水平以缓解脓毒症ALI大鼠肺损伤,可能与miR⁃223⁃3p/NLRP3通路有关。AIM To study the benefits of baicalin on rats with sepsis⁃induced acute lung injury(ALI)by regulating miR⁃223⁃3p/NOD⁃like receptor protein 3(NLRP3)pathway.METHODS After the establishment of some sepsis⁃induced ALI rat models,all rats were divided into sham operation group,model group,dexamethasone group,baicalin groups for low dose,moderate dose,and high dose uses.The rats were subjected to measurement of serum levels of TNF⁃α,IL⁃1β,IL⁃10 by ELISA;the observation of lung histopathology by HE staining;the determination of lung water content and AFC;and the identification of pulmonary levels of miR⁃223⁃3p and NLRP3 by RT⁃qPCR and Western blot,respectively.RESULTS Compared with the sham operation group,the model group demonstrated increased serum levels of IL⁃1βand TNF⁃α,WW/DW value and pulmonary level of NLRP3(P<0.05);and decreased serum IL⁃10 level,AFC value and pulmonary miR⁃223⁃3p level(P<0.05);destroyed alveoli integrity,collapsed alveoli,obviously edematous pulmonary interstitium,a large number of inflammatory cell infiltrates,and increased pulmonary pathological score(P<0.05).Baicalin treatment dose⁃dependently brought forth decrease of serum IL⁃1βand TNF⁃αlevels,WW/DW value and pulmonary NLRP3 level(P<0.05),and increase of serum IL⁃10 level,AFC value and pulmonary miR⁃223⁃3p level(P<0.05);recovered alveolar structure,relieved pulmonary interstitial edema,reduced inflammatory cell infiltrates,and lower pulmonary pathological score(P<0.05).CONCLUSION Baicalin can alleviate lung injury in sepsis⁃induced ALI in rats by down⁃regulating the levels of proinflammatory factors IL⁃1βand TNF⁃αand up⁃regulating the level of anti⁃inflammatory factor IL⁃10 via miR⁃223⁃3p/NLRP3 pathway.

关 键 词：黄芩苷 miR⁃223⁃3p NOD样受体蛋白3 脓毒症 急性肺损伤 

分 类 号：R285.5􀆰[医药卫生—中药学]