百里香醌对脂多糖诱导大鼠心肌纤维化的保护作用及机制研究
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篇名: 百里香醌对脂多糖诱导大鼠心肌纤维化的保护作用及机制研究
TITLE:
摘要: 目的:探讨百里香醌(TQ)对脂多糖(LPS)诱导的大鼠心肌纤维化(MF)的保护作用及其可能机制。方法:将40只雄性Wistar大鼠随机分为对照组、模型组和TQ低、高剂量组[5、10 mg/(kg·d)],每组10只。除对照组大鼠腹腔注射等体积生理盐水外,其余各组大鼠均腹腔注射LPS复制MF模型,每天1次,连续3周。自造模第1天起,各给药组大鼠均腹腔注射相应药物,每天1次,连续3周。末次给药后,采用酶联免疫吸附测定法(ELISA)检测各组大鼠血清炎症因子[白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)]含量;称定并计算其心脏质量参数[心脏质量指数(HW/BM)、左心室质量指数(LVW/BW)];采用苏木精-伊红染色法观察其心肌组织病理学变化;采用化学分析法、黄嘌呤氧化酶法或酶联免疫吸附法检测其心肌组织中氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)]和心肌胶原指标[羟脯氨酸(HYP)、Ⅰ型胶原蛋白(Col-Ⅰ)、Col-Ⅲ]含量或活性;采用实时荧光定量聚合酶链反应法检测其MF相关调控基因[Col-Ⅰ、Col-Ⅲ、基质金属蛋白酶3(MMP-3)、MMP-9、转化生长因子β1(TGF-β1)、Smad3]的mRNA表达情况。结果:与对照组比较,模型组大鼠心肌细胞肿胀,细胞核大小不一且排列紊乱,纤维增生明显;血清炎症因子含量,LVW/BW,心肌组织MDA、HYP、Col-Ⅰ、Col-Ⅲ含量以及Col-Ⅰ、Col-Ⅲ、TGF-β1、Smad3的mRNA相对表达量均显著升高(P<0.05),SOD活性显著降低(P<0.05)。与模型组比较,TQ各剂量组大鼠MF程度均有不同程度的改善;TQ低剂量组大鼠血清IL-1β含量,心肌组织MDA、HYP、Col-Ⅰ含量,TQ高剂量组大鼠血清IL-1β、IL-6、TNF-α含量,LVW/BW,心肌组织MDA、HYP、Col-Ⅰ、Col-Ⅲ含量以及TQ各剂量组Col-Ⅰ、Col-Ⅲ、TGF-β1的mRNA相对表达量均显著降低(P<0.05);TQ各剂量组心肌组织SOD活性显著升高(P<0.05)。其余指标组间比较差异均无统计学意义(P>0.05)。结论:TQ对MF模型大鼠具有一定的保护作用,其作用机制可能与抑制炎症反应和氧化应激反应,下调Col-Ⅰ、Col-Ⅲ、TGF-β1的mRNA表达有关。
ABSTRACT: OBJECTIVE: To investigate the protective effect and its mechanism of thymoquinone (TQ) on myocardial fibrosis (MF) induced by lipopolysaccharide in rats. METHODS: Totally 40 male Wistar rats were randomly divided into control group, model group, TQ low-dose and high-dose groups [5, 10 mg/(kg?d)], with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally, other groups were given LPS intraperitoneally to induce MF model, once a day, for consecutive 3 weeks. Since the first day of modeling, administration group was given relevant medicine intraperitoneally, once a day, for consecutive 3 weeks. After last medication, ELISA method was used to detect the contents of serum inflammation factors (IL-1β, IL-6, TNF-α) in rats. Cardiac mass parameters (HW/BM, LVW/BW) were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators (MDA, SOD) and myocardial collagen indexes (HYP, Col-Ⅰ, Col-Ⅲ) were detected by chemical analysis, xanthine oxidase method or ELISA. mRNA expression of regulation genes (Col-Ⅰ, Col-Ⅲ, MMP-3, MMP-9, TGF-β1 and Smad3) related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS: Compared with control group, there were swollen myocardial cells, disordered nuclei of different sizes and visible fiber hyperplasia in model group; the levels of serum inflammatory factors and LVW/BW, cardiac contents of MDA, HYP, Col-Ⅰand Col-Ⅲ, mRNA expression of Col-Ⅲ, TGF-β1 and Smad3 in model group were increased significantly (P<0.05), while SOD activity was decreased significantly (P<0.05). Compared with model group, the degree of myocardial fibrosis was improved in TQ groups to different extents; serum content of IL-1β and the contents of MDA, HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group, serum contents of IL-1β, IL-6 and TNF-α, LVW/BW and the contents of MDA, HYP, Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ, Col -Ⅲ, TGF-β1 in TQ groups were decreased significantly (P<0.05). The activities of SOD in cardiac tissue were increased significantly in TQ groups (P<0.05). There was no statistical significance in other indexes among groups (P>0.05). CONCLUSIONS: TQ can protect against MF model rats to certain extent, the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction, and down-regulation of mRNA expression of Col-Ⅰ, Col-Ⅲ and TGF-β1.
期刊: 2019年第30卷第4期
作者: 蔡伟,杨佳丹,高珊,李世琴,王述蓉
AUTHORS: CAI Wei,YANG Jiadan,GAO Shan,LI Shiqin,WANG Shurong
关键字: 百里香醌;脂多糖;心肌纤维化;炎症反应;氧化应激;调控基因;大鼠
KEYWORDS: Thymoquinone; Lipopolysaccharide; Myocardial fibrosis; Inflammatory reaction; Oxidative stress; Regulation genes; Rat
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