摘要
目的 通过肝脏能量代谢途径研究健脾化浊消脂方(JPHZXZF)防治代谢相关脂肪性肝病大鼠的作用机制.方法 将36只雄性SD大鼠随机分为空白组,模型组,阳性药物组,健脾化浊消脂方高、中、低剂量组.空白组饲喂维持饲料,其余五组饲喂高脂饲料同时饮用10%果葡糖浆溶液,连续喂养12周后,各给药组小鼠给予相应药物连续干预4周.末次给药后,采用生化分析仪测定大鼠血清中三酰甘油(TG)、总胆固醇(T-CHO)、低密度脂蛋白胆固醇(LDL-C)、空腹葡萄糖(FBG)含量;试剂盒法检测大鼠肝脏中TG、T-CHO、游离脂肪酸(NEFA)、柠檬酸合成酶(CS)、肉毒碱棕榈酸转移酶-1(CPT-1)、低氧诱导因子-1α(HIF-1α)、乳酸脱氢酶(LDH)含量或活性;用油红0、HE染色观察大鼠肝脏病理变化;采用蛋白免疫印迹法检测大鼠肝脏组织中p-AMPKα、HIF-1α蛋白表达水平.结果 JPHZXZF可以显著降低 TG、T-CHO、LDL-C、FBG、NEFA、CS、CPT-1、HIF-1α、LDH 含量或活性(P<0.05),缓解肝细胞脂质沉积,升高p-AMPKα的蛋白表达水平(P<0.05),降低HIF-1α的蛋白表达水平(P<0.05).结论 JPHZXZF可以有效改善代谢相关脂肪性肝病糖脂代谢紊乱,其作用可能与改变能量代谢途径有关.
Abstract
Objective To determine the mechanism of Jianpi Huazhuo Xiaozhi formula(JPHZXZF)in preventing and treating metabolism-related fatty liver diseases in rats via the hepatic energy metabolism pathway.Methods Totally 36 male SD rats were randomly divided into six groups:a blank group,a model group,a positive drug group,and JPHZXZF high-dose,medium-dose,and low-dose groups.The blank group was provided with a sustaining diet,the other five groups were given high fat diet and 10%high fructose corn syrup for 12 weeks continuously.Subsequently,each treatment group received corresponding medication for 4 weeks continuously.After the final administration,the content of triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein cholesterol(LDL-C)and fasting glucose(FBG)in the rat serum was determined by biochemical analyzer.The content or activity of TG,T-CHO,free fatty acid(NEFA),citrate synthase(CS),botulinum line palmitc transferase-1(CPT-1),hypoxia-1α(HIF-1α),and lactate dehydrogenase(LDH)in the rat liver was detected by the test kit.The liver pathological changes in the rats were observed with Oil Red O and HE staining.Western blot was used to detect the expression levels of p-AMPKα and HIF-1α.Results JPHZXZF significantly reduced the expression of TG,T-CHO,LDL-C,FBG,NEFA,CS,CPT-1,HIF-1α,and LDH(P<0.05),alleviated hepatocyte lipid deposition,increased the expression of p-AMPKα protein(P<0.05),and reduced the expression of HIF-1α protein(P<0.05).Conclusion JPHZXZF can effectively relieved glucose and lipid disorders in metabolism-related fatty liver diseases,whose mechanism may be related to the altered energy metabolic pathways.
基金项目
陕西省自然科学基础研究计划(2022JM-454)
陕西省中医药管理局"青年培优项目"(2021-PY-01)
国家中医药管理局第五批优秀中医研修人才(国中医药人教函2022-1号)
陕西省科学技术协会青年人才托举计划项目(20230310)
安康市科技局基金(AK2021-SFZC-06)
安康市科技局基金(AK2020-SF-06)