摘要
目的观察关节炎大鼠心功能的变化及雷公藤甲素的干预作用,探讨其可能的作用机制。方法将40只大鼠随机分为正常对照(NC)组、模型对照(MC)组、来氟米特(LEF)组和雷公藤甲素(TP)组。除NC组外,其余各组大鼠右后足跖皮内注射弗氏完全佐剂制备关节炎模型,制模第12天开始给药干预,TP组、LEF组大鼠分别灌胃其混悬液(TP0.1 mg/mL,LEF 0.5 mg/mL)1 mL/100 g (体质量),NC组、MC组大鼠相应时间灌胃等量的生理盐水,给药30 d。末次用药24 h后,采用左心室插管术检测大鼠心功能;应用酶联免疫吸附实验法测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)、总抗氧化能力(T-AOC)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平。采用荧光定量PCR法检测心组织Keap样蛋白1(Keap1)、肌腱膜纤维肉瘤(maf)、核因子-E2相关因子2(Nrf2)mRNA表达;采用Western blot法检测心组织Keap1、maf、Nrf2蛋白表达。结果①与NC组比较,MC组大鼠的心功能指标中心率(HR)、心脏指数(HI)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)升高,左心室压力上升和下降最大变化率(±dp/dtmax)降低(P均<0.01)。SOD、MDA、ROS、T-AOC、TNF-α升高,IL-10降低(P均<0.01)。心组织Keap1、maf、Nrf2 mRNA和蛋白表达均升高(P<0.01)。②与MC组比较,TP组大鼠HR、LVSP、HI、LVEDP降低,±dp/dtmax升高(P<0.01)。TNF-α、T-AOC、MDA、SOD、ROS下降,IL-10升高(P <0.05或P <0.01)。TP组大鼠心组织Keap1、maf、Nrf2 mRNA和蛋白表达降低(P<0.01)。结论 TP可改善关节炎大鼠心功能,其机制可能与提高心肌细胞抗氧化能力、减轻氧化应激损伤、抑制异常免疫炎症反应有关。
Objective To observe the changes of cardiac function in arthritic rats and the effect of triptolide on it. Methods Forty rats were divided in random into normal control(NC) group, model control(MC) group,leflunomide(LEF) group and triptolide(TP) group. Except for the normal group, rats in the other three groups were injected with Freund’s complete adjuvant to create arthritic inflammation in the right hind paws, and the interventional drug was administered on the 12 th day after the inflammation. By treating for 30 d, the cardiac function of rats was detected by left ventricular catheterization. The expressions of superoxide dismutase(SOD), malondialdehyde(MDA),reacitve oxygen species(ROS), total antioxidation(T-AOC), interleukin-10(IL-10) and tumor necrosis factor-α(TNF-α)in serum were measured by enzyme-linked immunosorbent assay. The expressions of keap-like protein 1(Keap1),muscular aponeurotic fibrosarcom(maf) and nuclear factor-E2 related factor2(Nrf2) mRNAs in cardiac tissue were detected by real-time PCR. The expressions of Keap1, maf and Nrf2 proteins in heart tissues were detected by Western blot. Results Comparing with the normal group, the heart rate(HR), heart index(HI), left ventricular systolic pressure(LVSP), and left ventricular end-diastolic pressure(LVEDP) of the model group were significantly increased, whereas the maximum change rate of ventricular pressure rise or decline(±dp/dtmax) was significantly decreased(P<0.01). SOD,MDA, ROS, T-AOC, and TNF-α were all increased, and IL-10 was significantly decreased(P<0.01). The mRNA and protein expressions of Keap1, maf and Nrf2 in heart tissues were increased(P<0.01). Comparing with the model group,HR, HI, LVSP, and LVEDP in the triptolide group were significantly decreased, whereas the ±dp/dtmax was significantly increased(P<0.01). SOD, MDA, T-AOC, ROS, TNF-α decreased while the IL-10 increased(P<0.05, P<0.01). The expressions of Keap1, maf and Nrf2 mRNAs and proteins in the heart tissues of the triptolide group were decreased(P<0.01). Conclusion Triptolide could improve cardiac function in arthritic rats, and the mechanism may related to its ability of improving the anti-oxidationin cardiomyocytes, reducing oxidative stress damage, and inhibiting abnormal immune inflammatory response.
作者
万磊
刘健
黄传兵
孙玥
张晓军
刘天阳
WAN Lei;LIU Jian;HUANG Chuan-bing;SUN Yue;ZHANG Xiao-jun;LIU Tian-yang(Department of Rheumatology,the First Affiliated Hospital,Anhui University of Chinese Medicine,Hefei 230031,China;Clinical Medicine College,Anhui University of Chinese Medicine,Hefei 230038,China)
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2020年第2期207-212,共6页
Journal of Sichuan University(Medical Sciences)
基金
科技部国家重点研发计划中医药现代化研究重点专项(No.2018YFC1705200,No.2018YFC1705204)
国家自然科学基金面上项目(No.81973655)
安徽省重点研究和开发计划对外科技合作项目(No.201904b11020011)
安徽省省级质量工程教学研究项目(No.2018jyxm1068)
安徽省名中医刘健工作室建设项目(中医药发展秘[2018]11号)
全国中医药创新骨干人才培训项目(国中医药人教函[2019]128号)
安徽省第12批“115”创新团队(皖人才办[2019]1号)
安徽省教育厅高校自然科学研究重点项目(No.KJ2018A0279)资助。
关键词
佐剂关节炎
心功能
氧化应激
雷公藤甲素
Adjuvant arthritis
Cardiac function
Oxidative stress
Triptolide