芒果苷单钠盐对高胆固醇血症大鼠肝脂质代谢及PCSK9/LDLR途径的影响

Effects of mangiferin monosodium salt on liver lipid metabolism and PCSK9/LDLR pathway in hypercholesterolemic rats

目的观察芒果苷单钠盐对高胆固醇血症大鼠肝脂质代谢及前蛋白转化酶枯草溶菌素9(PCSK9)/低密度脂蛋白受体(LDLR)的作用。方法选取SD大鼠40只,将其按体质量随机分为对照组、模型组、阿托伐他汀钙片组、芒果苷单钠盐组,每组10只。除对照组外,其余各组采用高脂饲料喂养法建立高胆固醇血症模型。造模成功后,阿托伐他汀钙片组ig阿托伐他汀钙片5 mg/kg,芒果苷单钠盐组ig 80 mg/kg芒果苷单钠盐,给药8周后,观察各组体质量及肝脏指数变化,生化法检测各组血脂指标[三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)],肾功能、血清酶指标[肌酐(CRE)、血清尿素(UREA)、肌酸激酶(CK)、乳酸脱氢酶(LDH)]及肝组织游离胆固醇(FC)、总胆汁酸(TBA)的含量,苏木精-伊红染色(HE)观察大鼠肝组织形态学变化,RT-PCR检测肝组织中白细胞介素-1β(IL-1β)和CD68 mRNA表达,Western blotting及RT-PCR检测肝组织中PCSK9、LDLR的蛋白及mRNA表达。结果与模型组相比,各给药组大鼠体质量和肝脏指数明显降低(P<0.05);血清中TC、LDL-C及CRE、UREA、CK、LDH水平显著降低,HDL-C水平显著升高(P<0.05);肝组织中FC含量降低,TBA含量升高(P<0.05);肝脏脂肪变性改善明显;肝组织I L-1β、CD68 mRNA表达明显减少(P<0.05),同时显著降低了PCSK9的蛋白和mRNA水平,提升了LDLR的蛋白和mRNA水平(P<0.05)。结论芒果苷单钠盐可有效调节高胆固醇血症大鼠肝胆固醇代谢,减轻高脂造成的心肾功能损害,其作用可能与调节肝脏PCSK9/LDLR信号通路的表达,改善脂质代谢紊乱相关。

Objective To observe the effects of mangiferin monosodium salt on hepatic lipid metabolism and PCSK9/LDLR in hypercholesterolemic rats.Methods Forty SD rats were selected and randomly divided into 4 groups according to their body mass:control group,model group,Atorvastatin Calcium Tablets group,and mangiferin monosodium salt group,with 10 rats in each group.In addition to the control group,the other groups were fed with high-fat diet to establish hypercholesterolemia model.After the establishment of the model,the Atorvastatin Calcium Tablets group was ig Atorvastatin Calcium Tablets 5 mg/kg,mangiferin group was ig mangiferin 80 mg/kg,mangiferin monosodium salt group was ig 80 mg/kg mangiferin monosodium salt,respectively.After 8 weeks of administration,observe the changes of body mass and liver index in each group.Detect the four items of blood lipids(TC,TG,LDL-C,HDL-C)in serum,renal function,serum enzyme indexes(CRE,UREA,CK,LDH),and the contents of FC and TBA in liver tissue by biochemical method.HE staining was used to observe the morphological changes of rat liver.The mRNA expression of IL-1βand CD68 in liver tissue were detected by RT-PCR.Western blotting and RT-PCR were used to detect the protein and mRNA expression of PCSK9 and LDLR in liver tissues.Results Compared with the model group,the body mass and liver index of rats in each group were significantly decreased(P<0.05).The levels of TC,LDL-C,CRE,UREA,CK,LDH in serum were significantly decreased,but HDL-C was increased(P<0.05).The content of FC in liver tissue was decreased,and the content of TBA was increased(P<0.05).The liver steatosis was significantly improved.mRNA Expression of IL-1βin liver tissue was significantly increased,and CD68 was significantly decreased(P<0.05).The protein and mRNA level of PCSK9 was significantly decreased,and the levels of LDLR was increased(P<0.05).Conclusion Mangiferin monosodium salt can effectively regulate the liver cholesterol metabolism in hypercholesterolemic rats and reduce the damage of heart and kidney function caused by hyperlipidemia,which may be related to regulating the expression of PCSK9/LDLR signal pathway in the liver and improving the disorder of lipid metabolism.