目的观察丹参、瓜蒌配伍对高脂血症小鼠及相关BMP/SMAD信号通路的影响,探讨其可能的调脂机制。方法 50只雄性Fpn1Tek-cre小鼠随机分为正常对照组、模型组、阿托伐他汀组、丹参组、瓜蒌组、丹参瓜蒌组,每组8只。高脂高胆固醇饲料喂养8周复制高脂血症模型。8周后,继续高脂喂养并按体重比折算的临床推荐剂量分别给予生理盐水、阿托伐他汀混悬液5.1 mg/kg、丹参组2.56 g/kg、瓜蒌组3.84 g/kg、丹参瓜蒌组6.4 g/kg。连续灌胃2周后,分离血清及肝组织。生化检测:TC、TG、LDL-C、HDL-C;酶联免疫吸附法测:血清铁调素、丙二醛(MDA)、超氧化物歧化酶(SOD)、白介素-6(IL-6);免疫组化法测肝组织骨形态发生蛋白(BMP6)表达量;Western blotting检测肝组织p-smad1/5/8,p-stat3蛋白表达。结果与空白组比较,模型组血清TC、TG、LDLC、铁调素(hepcidin)含量明显升高(P〈0.05),提示造模成功。与模型组比较,各用药组小鼠血清铁调素含量有不同程度下降(P〈0.05或P〈0.01);BMP6蛋白表达亦有所下降(P〈0.05)。与阿托伐他汀组比较,丹参瓜蒌组stat、smad蛋白磷酸化表达显著下降(P〈0.05)。与丹参组比较,丹参瓜蒌组明显降低TC、hepcidin水平(P〈0.05);与瓜蒌组比较,丹参瓜蒌组能显著降低TG、TC、铁调素水平(P〈0.05)。结论丹参、瓜蒌配伍通过调节小鼠铁调素降脂,其调脂机制为调节BMP/SMAD信号通路抑制铁调素表达。丹参瓜蒌配伍效果优于两药单独使用,为临床治疗痰浊血瘀型高脂血症提供了理论支持。
Objective To investigate the compatibility effects of Danshen and Gualou on hepcidin and its related bone morphogenetic protein( BMP) /Smad signal pathway in mice with hyperlipidemia induced by high-fat-diet,and to explore its possible mechanisms. Methods Fifty female Fpn1 Tek-cre mice were randomly divided into control group and model group. Eigh mice were fed with standard diet as control group,others were given high-fat-diet for 8 weeks to establish the hyperlipidemia models. After 8 weeks,the established mice were randomly divided into five groups and were intragastrically administered normal saline,atorvastatin suspension,Danshen decoction,Gualou decoction,Danshen Gualou decoction for 2 weeks,respectively. Blood was collected in sterile tubes,liver were removed and sacrificed by cervical dislocation,Serum lipids parameters were measured with an automated analyzer. The levels of interleukin-6( IL-6),hepcidin,malonaldehyde( MDA),superoxide dismutase( SOD) were determined by enzyme linked immunosorbent assay. The liver expression position of bone morphogenetic protein 6( BMP 6) was analysed by immunohistochemical method. Western blotting was to test the expressions of phosphorylation of Smad 1 /5 /8 and stat 3. Results Compared with the control group,the levels of total cholesterol( TC),triglyceride( TG),low density lipoprotein-cholesterol( LDL-C),hepcidin were increased in model groups(P 0. 05). Compared with model group,the levels of hepcidin and BMP 6 were decreased in treatment groups(P 0. 01 or P 0. 05). Compared with atorvastatin group,the expressions of phosphorylation of stat 3 and Smad were decreased in Danshen Gualou decoction group(P 0. 05). Compared with Danshen decoction group,the levels TC and hepcidin were decreased in Danshen Gualou decoction group(P 0. 05). Compared with Gualou decoction group,the levels of TG,TC and hepcidin were decreased in Danshen Gualou decoction group(P 0. 05). Conclusion Danshen and Gualou compatibility can regulate the