文章摘要
人参总皂苷急性毒性评价及其对肺损伤和肺纤维化模型小鼠的治疗作用
Acute toxicity evaluation of total ginsenosides and its therapeutic effect on lung injury and pulmonary fibrosis model mice
投稿时间:2024-11-19  修订日期:2024-12-27
DOI:
中文关键词: 人参总皂苷  急性毒性  雾化  肺损伤  肺纤维化
英文关键词: total ginsenoside,TG  acute toxicity  atomization  acute lung injury  pulmonary fibrosis
基金项目:浙江省院内制剂研发中医药传承创新团队(培育);浙江中医药大学2022年附属医院科研专项(No.2022FSYYZZ06);浙江中医药大学2022年附属医院科研专项(No.2022FSYYZZ34);浙江中医药大学2023年附属医院科研专项(No.2023FSYYZQ30)
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中文摘要:
      目的 评价人参总皂苷(total ginsenoside,TG)口服和雾化给药对小鼠的急性毒性,并评价其对急性肺损伤(acute lung injury,ALI)和肺纤维化(pulmonary fibrosis,PF)小鼠的治疗作用。方法 ICR雌雄小鼠分别雾化和口服最大剂量TG,14天后通过体重、血常规、血清生化、肺泡灌洗液(bronchoalveolar lavage fluid,BALF)分析、脏器指数和苏木素-伊红(H&E)染色评价TG的急性毒性。建立博来霉素(bleomycin,BLM)诱导的ALI和PF小鼠模型,以造模后第6天为ALI模型,第28天为PF模型。取BALF和肺脏,通过BALF分析、肺系数、羟脯氨酸(hydroxyproline,HYP)含量、H&E和Masson染色评价TG对ALI和PF的治疗作用。结果 急性毒性实验中,与对照组相比,雾化TG组和口服TG组在体重、脏器指数、血清生化、BALF分析中均无统计学差异,口服TG雄性组的外周血淋巴细胞数量减少,口服TG雌性组的外周血淋巴细胞数量增多,病理组织学上均未见明显异常。药效实验中,雾化TG对BLM诱导的ALI和PF小鼠具有良好的治疗作用,能有效减少BALF中的炎性细胞数量,降低肺系数和HYP含量,减少肺组织中的炎性浸润和纤维沉积,同等剂量条件下,雾化TG的疗效明显优于口服TG。结论 雾化TG无明显毒副作用且对BLM诱导的ALI小鼠和PF小鼠具有明显疗效。
英文摘要:
      Objective To evaluate the acute toxicity of oral and aerosol administration of total ginsenoside (TG) in mice, and to evaluate its therapeutic effect on acute lung injury (ALI) and pulmonary fibrosis (PF) in mice. Methods ICR male and female mice were atomized and orally administered with the maximum dose of TG, respectively. After 14 days, the acute toxicity of TG was evaluated by body weight, blood routine, serum biochemistry, bronchoalveolar lavage fluid (BALF) analysis, organ index and hematoxylin-eosin (H&E) staining. Bleomycin (BLM) -induced ALI and PF mouse models were established. The ALI model was established on the 6th day after modeling, and the PF model was established on the 28 th day. The therapeutic effects of TG on ALI and PF were evaluated by BALF analysis, lung coefficient, hydroxyproline (HYP) content, H&E and Masson staining. Results In the acute toxicity experiment, compared with the control group, there was no significant difference in body weight, organ index, serum biochemistry and BALF analysis between the atomized TG group and the oral TG group. The number of peripheral blood lymphocytes in the oral TG male group decreased, and the number of peripheral blood lymphocytes in the oral TG female group increased. There was no significant abnormality in histopathology. In the pharmacodynamic experiment, atomized TG has a good therapeutic effect on BLM-induced ALI and PF mice. It can effectively reduce the number of inflammatory cells in BALF, reduce lung coefficient and HYP content, and reduce inflammatory infiltration and fiber deposition in lung tissue. Under the same dose conditions, the efficacy of atomized TG is significantly better than that of oral TG. Conclusion Inhaled TG had no obvious toxic and side effects, and the inhaled administration route has a significant effect on BLM-induced ALI and PF.
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