沙苑子总黄酮对肾阳虚高脂血症模型大鼠血脂、甘油三酯合成途径的影响  

Influence of total flavonoids in Shayuanzi on blood fat level and synthesis pathway of triglyceride in rats with hyperlipidemia(kidney yang deficiency pattern)

作　　者：付璐 王景霞[1] 姚骏凯 唐潇然 贾岚 张建军[1] 高学敏[1] Fu Lu;Wang Jingxia;Yao Junkai;Tang Xiaoran;Jia Lan;Zhang Jian Jun;Gao Xuemin(Beijing University of Chinese Medicine, Beijing 100029, China)

机构地区：[1]北京中医药大学北京100029

出　　处：《北京中医药大学学报》2018年第1期31-38,共8页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81673617),北京中医药大学自主课题-中青年教师类(No.2016-JYB-JSMS-0003)

摘　　要：目的探讨沙苑子总黄酮(TFS)对肾阳虚高脂血症的治疗作用及其对肝脏甘油三酯(TG)合成途径的影响。方法 10周龄雌性SD大鼠,按体重随机区组法分为6组,即假手术组,模型组,雌激素组和TFS高、中、低剂量组,每组10只。双侧卵巢切除手术并连续给予6周高脂饲料复制肾阳虚高脂血症大鼠模型。假手术组和模型组灌胃生理盐水(10 m L/kg),雌激素组灌胃戊酸雌二醇(0.2 mg/kg),其余分别灌胃TFS 28.5、57、114 mg/kg,持续给药8周。检测血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),酶免法检测肝脏脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)活性和甘油三磷酸酰基转移酶(GPAT)、肉毒碱棕榈酰转移酶-1α(CPT-1α)、乙酰辅酶A氧化酶(ACO)水平,免疫组化法检测肝脏固醇调控元件结合蛋白-1c(SREBP-1c)、过氧化物酶体增殖物激活受体α(PPARα)蛋白表达。结果与模型组相比,TFS高剂量组大鼠血清TG、TC、LDL-C水平显著降低(P<0.05,P<0.01),血清HDL-C水平显著升高(P<0.05);肝脏ACC活性和GPAT水平显著降低(P<0.01,P<0.01),ACO、CPT-1α水平显著升高(P<0.01,P<0.05);肝细胞膜SREBP-1c蛋白表达量显著降低,肝细胞核PPARα蛋白表达量显著增加。结论实验结果表明TFS具有良好的调节血脂代谢的作用,其作用机制可能是通过抑制肝脏SREBP-1c表达,降低TG合成途径中限速酶FAS、ACC、GPAT的活性及水平;上调PPARα蛋白表达,提高脂肪酸β氧化途径中ACO、CPT-1α的表达水平,两者共同发挥作用抑制肝脏中TG的合成,达到调脂作用。Objective To investigate the therapeutic effect of total flavonoids in Shayuanzi （Semen Astragali Complanati, flatstem milkvetch seed, TFS ） on hyperlipidemia （kidney yang deficiency pattern） and their influence on liver synthesis pathway of triglyceride （TG）. Methods SD rats （10 weeks old） were divided, according to weight randomized block method, into 6 groups： sham-operation group, model gToup, estrogen group, high-dose TFS group, mid-dose TFS group） and low-dose TFS group （each n = 10）. The rat model of hyperlipidemia （kidney yang deficiency pattern） was copied by bilateral ovariectomization and high fat diet for 6 weeks. The sham-operation group and model group were intragastrically given normal saline （10 mL/kg）, estrogen group, estradiol （0.2 mg/kg）, and TFS groups, total flavonoids in Shayuanzi （28.5 mg/kg, 57 mg/kg and 114 mg/kg respectively ） for 8 weeks. The levels of triglyceride （TG）, total cholesterol （TC）, low-density lipoprotein-cholesterol （LDL-C） and high-density lipoprotein-cholesterol （HDL-C） were detected. The activities of liver fatty acid synthase （FAS） and acctyl-CoA carboxylase （ACC）, and levels of GPAT, CPT-1α and acy-CoA oxidase （ACO） were detected by using enzyme immunoassay （EIA）. The protein expressions of sterol regulatory element-binding protein-lc （SREBP-1c） and peroxisome proliferator-activiated receptor-α （PPAR-u） were detected by using immunohistochemistry technique. ResuitsCompared with model group, the levels of serum TG, TC and LDL-C decreased significantly （P 〈0. 05, P 〈 0.01 ） , level of serum HDL-C increased significantly （ P 〈 0.05 ）, activities of liver ACC and GPAT level decreased significantly （P 〈 0.01, P 〈 0.01 ） , levels of ACO and CPT-1α increased significantly （P 〈 0.01, P 〈 0.05 ）, protein expression of SREBP-lc was significantly down-regulated, and protein expression of PPAR-α was significantly up-regulated in high-dose TFS group. Conclusion TFS has

关 键 词：沙苑子总黄酮 肾阳虚 高脂血症 固醇调控元件结合蛋白-1c 过氧化物酶体增殖物激活 体α 大鼠 

分 类 号：R285.5[医药卫生—中药学]