荷丹三七降脂片对高脂血症大鼠脂代谢及Nrf2、γ-GCS基因mRNA表达的影响

Effects of Hedan Sanqi Jiangzhitablet on lipid metabolism and Nrf2, γ-GCS gene mRNA expression in rats with hyperlipidemia

目的:探讨荷丹三七降脂片对高脂血症大鼠血脂代谢的影响。方法:将72只大鼠随机分为正常对照组、高脂血症模型组、荷丹三七降脂片高剂量组、中剂量组、低剂量组、阳性对照组(辛伐他汀)6个小组,每小组12只。采用高脂饲料建立大鼠高脂血症模型,连续给药30 d后,测体质量、肝脏湿重和肝脏系数;取血测定各剂量组高脂血症大鼠血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷草转氨酶(AST)、谷丙转氨酶(ALT)水平;测定肝组织的抗氧化指标:超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、总抗氧化能力(T-AOC);采用实时荧光定量RT-PCR法测定高脂血症大鼠肝组织中核因子NF-E2相关因子(nuclear factor erythroid 2-related factor2,Nrf2)、谷氨酰半胱氨酸合酶(γ-glutamylcysteine synthethase,γ-GCS)mRNA表达;显微镜下观察肝组织形态学变化;通过小鼠急性毒性试验记录小鼠状况。结果:与模型组比较,荷丹三七降脂片各剂量组显著降低TC、TG、LDL-C、MDA水平(P<0.01,P<0.05);显著升高SOD、CAT、GSH-Px、T-AOC(P<0.01,P<0.05)以及肝组织中的Nrf2、γ-GCS mRNA表达显著升高(P<0.01,P<0.05)并明显减轻肝组织病理损伤;急性毒性试验表明荷丹三七降脂片无毒性。结论:荷丹三七降脂片安全无毒,对高脂血症大鼠具有良好的辅助降血脂及肝脏保护作用,其可能作用机制是通过调节Nrf2基因表达的作用,促进γ-GCS表达,进而启动机体的抗氧化防御系统,减轻氧化应激对机体的损害作用。

OBJECTIVE To investigate the effects of Hedan Sanqi Jiangzhi Tablet on blood lipid metabolism in rats with hyperlipidemia.METHODS 72 rats were randomly divided into normal control group,hyperlipidemia model group,Hedan Sanqi Jiangzhi Tablet high dose group,middle dose group,low dose group and positive control group(simvastatin),with 12 rats in each group.A rat model of hyperlipidemia was established using high-fat diet.After 30 days of continuous administration,body weight,liver wet weight and liver coefficient were measured;Blood samples were taken to determine Total Cholesterol(TC),Triglyceride(TG),High-density lipoprotein cholesterol(HDL-C),Low-density lipoprotein cholesterol(LDL-C),Aspartate aminotransferase(AST),Alanine aminotransferase(ALT)levels in the serum of hyperlipidemic rats in each dose group;Determination of antioxidant indices in liver tissue:Superoxide dismutase(SOD),Malondialdehyde(MDA),Glutathione peroxidase(GSH-Px),Catalase(CAT),Total antioxidant capacity(T-AOC);Nuclear factor NF-e2-related factor(Nrf2)and glutathione-cysteine synthase(γ-glutamylcysteine synthethase)were measured by real-time quantitative RT-PCR in the liver of hyperlipidemic rats.γ-GCS mRNA expression;Morphological changes of liver tissue were observed under microscope;The status of rats was recorded by mouse acute toxicity test.RESULTS Compared with the model group,the doses of TC,TG,LDL-C and MDA were significantly decreased in each dose group of Hedan Sanqi Jiangzhi Tablet(P<0.01,P<0.05);SOD,CAT,GSH-Px were significantly increased.T-AOC(P<0.01,P<0.05)and Nrf2,γ-GCS mRNA expression in liver tissue were significantly increased(P<0.01,P<0.05)and significantly reduced liver tissue pathological damage;The acute toxicity test showed that the Hedan Sanqi Jiangzhi Tablet were non-toxic.CONCLUSION Hedan Sanqi Jiangzhi Tablet is safe and non-toxic,and has a good auxiliary effect on lowering blood lipid and protecting liver in rats with hyperlipidemia.Its mechanism may be through regulating the expression of Nrf2 gene,promoting the expression ofγ-GCS,thereby activating the antioxidant defense system of the body and reducing the damage of oxidative stress to the body.