[关键词]
[摘要]
目的 观察龙钻颗粒对心肌梗死模型大鼠心功能及核转录因子-κB(NF-κB)介导的炎症反应的影响,探究其对梗死心肌的保护作用及其机制。方法 采用结扎冠状动脉左前降支的方法制备大鼠心肌梗死模型,假手术组不结扎只穿针,将造模成功的大鼠随机分为5组:模型组、缬沙坦组(10 mg/kg)和龙钻颗粒高、中、低剂量(19.00、9.50、4.75 g/kg)组,每组10只,每天ig给药1次,连续28 d。通过超声心动图和血流动力学检测大鼠左心室射血分数(EF)、短轴缩短率(FS)、最大上升下降速率(±dp/dtmax)变化,以ELISA法测定各组大鼠血清中白细胞介素-6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)的水平,并采用qRT-PCR定量检测心肌组织中IL-6、TNF-α mRNA表达水平。采用蛋白印迹法检测NF-κB P65、p-P65的蛋白表达水平。结果 与模型组比较,龙钻颗粒能显著提高大鼠左心室EF和FS,改善血流动力学;龙钻颗粒高、中、低剂量组大鼠血清IL-6、IL-1β、TNF-α及CRP水平均显著降低(P<0.05、0.01),心肌组织中IL-6、TNF-α mRNA表达量也呈降低趋势(P<0.05、0.01)。龙钻颗粒能显著抑制NF-κB p-P65的表达(P<0.05、0.01)。结论 龙钻颗粒能够改善心肌梗死模型大鼠的心肌损伤,增强左心室功能,减轻炎症反应,其机制可能与NF-κB信号通路介导的炎症反应相关。
[Key word]
[Abstract]
Objective To observe the effects of Longzuan Granules (LZG) on cardiac function and the inflammatory reaction mediated by nuclear factor-κB (NF-κB) in myocardial infarction (MI) rats, and explore the protective effect on MI and its mechanisms. Methods The MI model was established by ligating the left anterior descending coronary artery of SD rats, sham group was only threading without ligation. The rat models were randomly divided into five groups:model group, Valsartan group (10 mg/kg), high-, medium-, and low-dose LZG (19.00 g/kg, 9.50 g/kg, and 4.75 g/kg) groups, with 10 rats in each group, ig administered once daily for 28 consecutive days. Changes in left ventricular function (EF%, FS%, and ±dp/dtmax) were detected by echocardiography and hemodynamics. The levels of inflammatory cytokines IL-6, IL-1β, TNF-α, and CRP in serum were measured by ELISA, and the mRNA expressions of IL-6 and TNF-α in cardiac tissues were detected by qRT-PCR. The protein expression levels of NF-κB P65 and p-P65 were detected by Western blotting. Results Compared with the model group, LZG significantly improved left ventricular function in rats; The serum levels of IL-6, IL-1β, TNF-α, and CRP decreased significantly (P < 0.05, 0.01) in LZG groups, the mRNA expressions of IL-6 and TNF-α in the cardiac tissues was also decreased (P < 0.05, 0.01). LZG significantly decreased the protein expression levels of NF-κB p-P65 (P < 0.05, 0.01). Conclusion LZG can improve myocardial injury, enhance the left ventricular function, and reduce the inflammatory reaction in MI rats, and its mechanism may be related to the inflammatory response through NF-κB signaling pathway.
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[基金项目]
国家自然科学基金资助项目(81460765,81674097);广西高校壮医方药基础与应用研究重点实验室课题(桂教科研[2016]6号zyfy201612);