桂枝汤联合限制热量饮食对高脂血症动物血脂的调节作用及机制研究

Regulatory effect on hyperlipidemia in animals and the mechanism of guizhi tang and calorie-control diet

目的研究桂枝汤联合限制热量饮食对高脂饮食诱导的高脂血症大鼠血脂的影响,并探讨这种联合治疗对肝脏氧化应激指标及核因子E2相关因子2/抗氧化反应原件(Nrf2/ARE)信号通路的影响。方法50只动物随机分为正常组(NC组)、模型组(HR组)、限制饮食组(CRT组)和限制饮食加桂枝汤联合治疗组(COM组)。除了正常组给予正常饲料喂养外,其余各组均给予高脂饲料喂养5周造模,造模成功后,NC组和HR组给予正常饮食,CRT组接受3 d的简单热量摄入限制,COM组联合热量限制和桂枝汤灌胃3 d。测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白的含量(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量。利用荧光定量PCR法测定肝脏组织中Nrf2及HO-1 mRNA表达含量。结果与NC组比较,HR组TC、TG、LDL-C显著增高(P<0.01),而HDL-C无显著性变化。与HR组相比,COM组TC、TG、HDL-C显著降低(P<0.01),LDL-C显著升高(P<0.05);CRT组TC、TG、HDL-C显著降低(P<0.05)。与NC组相比,HR组肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)和超敏C反应蛋白(Hs-CRP)水平明显升高(P<0.05)。与HR组相比,CRT组和COM组IL-6和Hs-CRP水平呈现下降趋势,但差异无统计学意义(P>0.05)。与HR组相比,COM组肝脏组织中Nrf2及HO-1表达含量显著升高(P<0.05)。结论桂枝汤联用限制热量饮食能明显改善大鼠血脂代谢的各项指标,降低总胆固醇、甘油三脂、低密度脂蛋白胆固醇,对高密度脂蛋白胆固醇水平有升高趋势,桂枝汤联合限制热量饮食治疗能提高抗氧化能力,与激活Nrf2/ARE通路有关。

Objective To explore the effect on blood lipid in the rats with hyperlipidemia with guizhi tang and calorie-control diet and the effect of this combined therapy on liver oxidative stress index and Nrf2/ARE(nuclear factor erythroid-2-related factor 2(Nrf2)/antioxidant response element) signal path. Methods A total of 50 animals were randomized into a normal group,a model group,a diet control group and a combined therapy group(guizhi tang + diet control). Except in the normal group fed with regular forage,the high-fat forage was used in the rest groups for model preparation for 5 weeks. After modeling success,the regular feeding was used in the normal group and model group. The calorie control was provided in the diet control group for 3 days. In the combined therapy group,the lavage with guizhi tang was combined with the calorie control for 3 days. The levels of TC,TG,HDL-C and LDL-C were determined. The fluorescent quantitation PCR method was adopted to determine the mRNA expressions of Nrf2 and HO-1 in liver tissue. Results Compared with the normal group,TC,TG and LDL-C were increased significantly in the model group(P < 0. 01) and HDL-C did not change obviously. Compared with the model group,in the combined therapy group,TC,TG and HDL-C were increased significantly(P < 0. 05) and TC,TG and HDL-C were reduced significantly in the diet control group(P <0. 05). Compared with the normal group,TNF-α,IL-6 and Hs-CRP were increased obviously in the model group(P <0. 05). Compared with the model group,in the diet control group and the combined therapy group,IL-6 and Hs-CRP were reduced in tendency,but without significant difference(P > 0. 05). Compared with the model group,the expressions of Nrf2 and HO-1 in liver tissue were increased significantly in the combined therapy group(P < 0. 05). Conclusion The combined treatment with guizhi tang and calorie control diet obviously improves in every index of blood lipid metabolism,reduces TC,TG and LDL-C and increases in tendency HDL-C. Such combined treatment improves the anti-oxidant capacity,which is related to the activation of Nrf2/ARE path.