摘要
目的 探讨天麻素改善大鼠肾性高血压作用机制。方法 75只SD雄性大鼠随机分为5组(n=15):假手术组、肾性高血压模型组、模型+雷米普利(1 mg·kg^(-1))组和模型+天麻素(100和200 mg·kg^(-1))组。通过结扎肾动脉构建肾性高血压大鼠模型,以尾动脉收缩压>18.12 kPa为造模成功。造模成功后,给药组大鼠分别ig给予相应剂量的雷米普利或天麻素,连续4周。采用比色法检测大鼠血清超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,采用ELISA检测血清血管紧张素2(Ang-2)和醛固酮(ALD)含量及血清和胸主动脉组织白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)含量,HE染色观察大鼠主动脉病理结构的改变。Western印迹法检测大鼠主动脉组织自噬蛋白微管相关蛋白轻链3Ⅱ(LC3-Ⅱ)与LC3-Ⅰ的比值(LC3-Ⅱ/LC3-Ⅰ)。结果 与假手术组比较,模型组大鼠血清Ang-2含量显著升高(P<0.01),ALD显著降低(P<0.01);血清和主动脉组织SOD活性显著降低(P<0.01),MDA含量显著升高(P<0.01),IL-1β,IL-6和TNF-α含量均显著升高(P<0.01);胸主动脉壁增厚且炎症细胞浸润,自噬蛋白LC3-Ⅱ/LC3-Ⅰ比值显著升高(P<0.01)。与模型组比较,模型+天麻素(100和200 mg·kg^(-1))组大鼠尾动脉收缩压显著降低(P<0.01);血清Ang-2含量显著降低(P<0.01),ALD含量升高(P<0.01),血清SOD活性增加(P<0.01);血清和主动脉组织MDA,IL-1β,IL-6和TNF-α含量降低(P<0.01);大鼠主动脉组织病理改变改善,同时LC3-Ⅱ/LC3-Ⅰ降低(P<0.01)。结论 天麻素可改善肾性高血压模型大鼠血压,其机制可能与降低LC3-Ⅱ/LC3-Ⅰ比值有关。
OBJECTIVE To explore the mechanism by which gastrodin improves renal hyperten-sion in rats.METHODS A rat model of renal hypertension was established by ligating the renal artery.seventy-five rats were randomly divided into 5 groups(n=15):control group(sham operation group),model group,model+ramipril 1 mg·kg^(-1),model+gastrodin 100 and 200 mg·kg^(-1).The systolic blood pressure of the tail artery after modeling>18.12 kPa was regarded as the success of modeling.After the model was established,rats in the model+ramipril group were ig given ramipril 1 mg·kg^(-1) while the model+gastrodin group was ig given gastrodin 100 and 200 mg·kg^(-1) respectively for 4 weeks.Colori-metric assay kit was used to detect the serum superoxide dismutase(SOD)activity and malondialde-hyde(MDA)content in rats.ELISA was used to detect serum angiotensin-2(Ang-2)and aldosterone(ALD)contents,as well as serum and thoracic aortic tissue interleukin-1β(IL-1β),IL-6 and tumor necrosis factorα(TNF-α)content.HE staining was performed to detect pathological changes in thoracic aorta tissue of rats.The expressions of autophagy protein miceotubule associated protein light chain 3(LC3)-Ⅱand LC3-Ⅰwere detected by Western blotting.RESULTS The systolic pressure of the tail artery of rats after modeling exceeded 18.12 kPa,indicating that the modeling was successful.Compared with the control group,the contens of Ang-2(P<0.01)and ALD(P<0.01)in the model group were significantly increased,the activity of SOD(P<0.01)in serum and thoracic aorta tissue was significantly decreased,the content of MDA(P<0.01)was significantly increased,the contents of IL-1β,IL-6 and TNF-αin serum and thoracic aorta tissue were significantly decreased(P<0.01)and the ratio of LC-32/LC-31 in thoracic aorta tissue was significantly increased(P<0.01).Compared with the model group,gastrodin significantly increased the systolic pressure of the tail artery(P<0.01),the contents of Ang-2(P<0.01)and ALD(P<0.01)and the activity of SOD(P<0.01)in serum,as well as decreased the contents of MDA,IL-1β,IL-6 and TNF-α(P<0.01)in serum and thoracic aorta tissue.Meanwhile,gastrodin signifi-cantly decreased the ratio of LC3-Ⅱ/LC3-Ⅰin rat thoracic aorta(P<0.01).CONCLUSION Gastrodin can improve the blood pressure of renal hypertensive rats,and the mechanism is possibly related to the reduction of autophagy protein LC3-Ⅱ/LC3-Ⅰratio.
作者
司丽芳
赵天智
宋毓民
李梦云
李翔
王飞耀
SI Lifang;ZHAO Tianzhi;SONG Yumin;LI Mengyun;LI Xiang;WANG Feiyao(College of Animal Science and Technology,Henan University of Science and Technology,Luoyang 471023,China;College of Animal Sciences,Dali Agriculture and Forestry Vocational and Technical College,Dali 671000,China;Linyi Vocational College of Science and Technology,Linyi 276000,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2024年第5期369-374,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(31401209)
河南科技大学青年科学基金(2019Qn024)
河南科技大学重大校企合作项目(2020XQ39)
动物营养调控与健康安徽省重点实验室基金(APKLANRH202004)。
关键词
天麻素
肾性高血压
主动脉
自噬
gastrodin
renal hypertension
thoracic aorta
autophagy
