亚高原地区野百合碱诱导大鼠肺动脉高压模型的剂量研究  

Dose Research of Monocrotaline Induced Pulmonary Arterial Hypertension in Rats at Moderate Altitude

作　　者：陈婷婷 杨占婷[1] 华玉美多 冀磊 顾存林[1,2] 王珊[1] 张小楠[1] 南星梅 李占强[1,2] 芦殿香[1,2] CHEN Tingting;YANG Zhanting;HUAYU Meiduo;JI Lei;GU Cunlin;WANG Shan;ZHANG Xiaonan;NAN Xingmei;LI Zhanqiang;LU Dianxiang(Qinghai University,Research Center for High Altitude Medicine,Key Laboratory of High Altitude Medicine(Ministry of Education),Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province(Qinghai-Utah Joint Research Key Lab for High Altitude Medicine),Xining 810001,China;Qinghai University,College of Medical,Xining 810001,China)

机构地区：[1]青海大学高原医学研究中心,高原医学教育部重点实验室,青海省高原医学应用基础重点实验室(青海-犹他高原医学联合重点实验室),西宁810001 [2]青海大学医学院,西宁810001

出　　处：《中国现代应用药学》2021年第21期2625-2631,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(82060786,81860768,32060088);青海省科技计划项目(2020-ZJ-784);中科院兰州分院“西部之光”立项项目。

摘　　要：目的探讨亚高原地区野百合碱(monocrotaline,MCT)诱导大鼠肺动脉高压模型的最佳剂量。方法将从平原地区购买85只♂SD大鼠随机分为对照组、MCT-20 mg·kg^(-1)组、MCT-30 mg·kg^(-1)组、MCT-40 mg·kg^(-1)组、MCT-50 mg·kg^(-1)组、MCT-60 mg·kg^(-1)组。除对照组外,所有大鼠于同日接受单次不同浓度MCT皮下注射,随后置于亚高原地区饲养,MCT注射第28天末采用右心导管术检测大鼠平均肺动脉压力,并计算大鼠右心室肥厚指数以评估右心肥厚程度,取大鼠肺组织行HE染色以评价肺血管重构情况,同时将大鼠的一般情况、生存率、体质量变化、脏器系数、血液学指标和模型成功率作为辅助评价指标。结果与对照组比较,单次皮下注射MCT-30,40,50,60 mg·kg^(-1)均可引起大鼠平均肺动脉压力增高、右心室肥厚和血管重构(P<0.05),模型符合肺动脉高压诊断标准。结论30 mg·kg^(-1)是亚高原地区MCT诱导大鼠肺动脉高压模型的最佳剂量。OBJECTIVE To explore the optimal dose of monocrotaline(MCT)induced pulmonary arterial hypertension in rats at moderate altitude.METHODS Eighty-five male SD rats were randomly divided into control group,MCT-20 mg·kg^(-1) group,MCT-30 mg·kg^(-1) group,MCT-40 mg·kg^(-1) group,MCT-50 mg·kg^(-1) group and MCT-60 mg·kg^(-1) group.Except for the control group,all rats received a single subcutaneous injection of MCT,and then were raised in moderate altitude area.Right heart catheterization was used to determine the mean pulmonary artery pressure(mPAP)after 28 d.The right ventricular hypertrophy index was calculated as a parameter of right ventricular hypertrophy.Vascular remodeling was assessed by HE staining.In addition,the general condition,survival rate,body weight,organ coefficient,hematological indexes and success rate of the model in rats were used as auxiliary evaluation indexes.RESULTS Compared with the control group,single subcutaneous injection of MCT-30,40,50,60 mg·kg^(-1) could cause increased mPAP,right ventricular hypertrophy and vascular remodeling in rats(P<0.05).The model met the diagnostic criteria for pulmonary arterial hypertension.CONCLUSION MCT-30 mg·kg^(-1) is the optimal dose to induce pulmonary arterial hypertension in rats at moderate altitude.

关 键 词：亚高原 野百合碱 大鼠 肺动脉高压 剂量研究 

分 类 号：R285.5[医药卫生—中药学]