机构地区:[1]平顶山学院,河南平顶山467000 [2]中国科学院藏药研究重点实验室中国科学院西北高原生物研究所,青海西宁810001 [3]中国科学院大学,北京100049 [4]东莞市金美济药业有限公司,广东东莞523808
出 处:《中药新药与临床药理》2021年第4期461-466,共6页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:青海省科技项目(2021-HZ-806);西宁市科技项目(2018-Y-23);2017年平顶山学院青年科研基金项目(PXYQNJJ2017009)。
摘 要:目的探讨五脉绿绒蒿总生物碱对脂多糖(LPS)诱导的小鼠炎症模型的抗炎作用及其机制。方法将BALB/c小鼠随机分为9组,即正常对照组、模型组(腹腔注射LPS 5 mg·kg^(-1))、头孢克洛组(阳性对照药,50 mg·kg^(-1)),以及五脉绿绒蒿总生物碱低、中、高剂量(20、50、100 mg·kg^(-1))治疗组与保护组,每组9只。治疗组在注射LPS的同时以相应剂量灌胃给药1次;保护组在腹腔注射LPS前1周开始灌胃给药,每天1次,连续7 d。对小鼠外周血白细胞及肺组织浸润炎性细胞进行计数;采用ELISA法检测血清肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的水平;紫外-可见分光光度法检测小鼠巨噬细胞分泌一氧化氮(NO)的含量及一氧化氮合酶(iNOS)活力;HE染色法进行小鼠肺组织病理学观察。结果与正常对照组比较,模型组小鼠在腹腔注射LPS后6、12 h的外周血白细胞数量及肺组织炎性细胞浸润数量明显增加(P<0.05),血清促炎因子TNF-α、IL-6水平显著升高(P<0.05,P<0.01);模型组小鼠可见肺组织充血,肺泡间质有炎性浸润,伴有肺泡腔出血和渗出;腹腔巨噬细胞上清液中的NO含量及iNOS活力明显提高(P<0.01)。与模型组比较,注射LPS后6 h,五脉绿绒蒿总生物碱高剂量保护组及各剂量治疗组的白细胞数量明显降低(P<0.05);注射LPS后12 h,各给药组的白细胞数量均明显降低(P<0.05);各给药组小鼠在注射LPS后6、12 h的肺组织炎性细胞浸润数量明显降低(P<0.05),血清TNF-α水平均明显降低(P<0.05);五脉绿绒蒿总生物碱高剂量保护组及治疗组在注射LPS后12 h的血清IL-6水平明显降低(P<0.05);各给药组小鼠肺组织的炎性病理改变明显减轻;五脉绿绒蒿总生物碱各剂量组的小鼠腹腔巨噬细胞上清液中的NO含量及iNOS活力明显降低(P<0.05)。与治疗组比较,五脉绿绒蒿总生物碱各保护组小鼠在注射LPS后6、12 h的血清TNF-α水平均明显降低(P<0.05)。结论五脉绿绒蒿Objective To study the anti-inflammatory effects and mechanism of ethanol extraction of total alkaloids from Meconopsis quintuplinervia Regel. on lipopolysaccharide(LPS)-induced inflammation in mice. Methods BALB/c mice were divided into 9 groups, namely normal control group, model control(ip, LPS, 5 mg·kg^(-1)) group,cefaclor treatment group(positive control, 50 mg · kg^(-1)), total alkaloids of Meconopsis quinluplinervia(20, 50,100 mg·kg^(-1))protection group and treatment group,each group has 9 animals. The treatment group was given the corresponding dose of intragastric administration once at the same time as the injection of LPS;the protection group was given intragastric administration 1 week before the intraperitoneal injection of LPS,once a day for 7 consecutive days. The peripheral blood leukocytes and lung tissue infiltrating inflammatory cells of mice in each group were counted. ELISA method was used to detect serum tumor necrosis factor alpha(TNF-α)and interleukin 6(IL-6)levels. Ultraviolet-visible spectrophotometry was used to detect the content of nitric oxide(NO)secreted by mouse macrophages and the activity of nitric oxide synthase(iNOS). The HE staining method was used to observe the pathology of mouse lung tissue. Results Compared with the normal control group,the number of peripheral blood leukocytes and the number of inflammatory cell infiltration in lung tissue in the model group increased significantly at6 and 12 h after intraperitoneal injection of LPS(P<0.05),and the levels of TNF-α and IL-6 were significantly increased(P<0.05,P<0.01). Lung tissue congestion,alveolar interstitial inflammatory infiltration,accompanied by alveolar hemorrhage and exudation were observed in the model group mice, and the contents of NO and the activity of iNOS in the supernatant of peritoneal macrophages were significantly increased(P<0.01). Compared with the model group,6 hours after injection of LPS,the number of white blood cells in the high-dose protection group of total alkaloids of Meconopsis quinque
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