[关键词]
[摘要]
目的 探讨葛根芩连汤对胰岛素抵抗(IR)大鼠肝脏能量代谢及游离脂肪酸(FFA)的影响。方法 采用 60% 脂肪的高脂饲料连续喂养13 周复制IR 大鼠模型。将SD 大鼠随机分为正常组、模型组、罗格列酮 组(5 mg·kg-1)以及葛根芩连汤低、中、高剂量组(1.65、4.96、14.86 g·kg-1),每组6 只。灌胃给药,每天1 次, 连续给药干预16 周。测定IR 相关指标:血清空腹胰岛素(FINS)、空腹血糖(FPG)值,计算IR 指数;建立 HPLC 法测定大鼠肝组织中三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)含量;采用ELISA 法测 定大鼠肝组织中的FFA 含量;采用全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)含量;采用HE 染色法观察肝脏组织病理变化。结果(1)模型复制结束后,与正常组比较,模型组大鼠的FINS、FPG 水平及 IR 指数显著升高(P<0.01);肝脏组织中ATP、ADP、AMP、FFA 含量均无明显变化(P>0.05)。(2)给药干预结 束后,与正常组比较,模型组大鼠的FINS、FPG 水平及IR 指数显著升高(P<0.01),肝脏组织中ATP、ADP、 AMP 含量均显著下降(P<0.01),FFA 含量显著升高(P<0.01),血清TC、TG 水平均明显升高(P<0.05);肝 细胞排列紊乱,出现脂肪变性,并存在大量脂滴。与模型组比较,各给药组大鼠的FINS 水平及IR 指数均明 显降低(P<0.05,P<0.01),罗格列酮组大鼠的FPG 水平明显降低(P<0.05);各给药组大鼠肝脏组织中ADP、 AMP 含量均明显升高(P<0.05、P<0.01),葛根芩连汤低、中、高剂量组大鼠肝脏组织中ATP 含量明显升高 (P<0.05、P<0.01);罗格列酮组及葛根芩连汤低、高剂量组大鼠肝脏组织中FFA 含量均显著降低(P<0.01); 葛根芩连汤低、高剂量组大鼠血清TC 水平明显降低(P<0.05,P<0.01),罗格列酮组及葛根芩连汤低剂量组 大鼠血清TG 水平明显降低(P<0.05,P<0.01);各给药组大鼠的肝细胞脂肪变性有不同程度减轻,且脂滴减 少,病理损伤得到改善。结论 葛根芩连汤可能通过调节能量代谢并降低FFA 水平,从而改善肝脏脂质代谢 紊乱,恢复脂质与能量平衡,从而起到改善IR 的作用。
[Key word]
[Abstract]
Abstract:Objective To investigate the effect of Gegen Qinlian Decoction on liver energy metabolism and free fatty acid (FFA) in rats with insulin resistance (IR). Methods IR rat model was established by feeding 60% fat high- fat diet for 13 consecutive weeks. SD rats were randomly divided into normal group, model group, Rosiglitazone (5 mg·kg-1) group and Gegen Qinlian Decoction low-,medium- and high- dose groups(1.65,4.96,14.86 g·kg-1), with 6 rats in each group. Intragastric administration was given once a day, continuous administration intervention lasted for 16 weeks. Determination of IR-related indicators: serum fasting insulin (FINS), fasting blood glucose (FPG), calculate the IR index; HPLC method was established for the determination of adenosine triphosphate (ATP),adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in rat liver tissue;ELISA was used to determine the content of FFA in rat liver tissue. The contents of serum total cholesterol (TC) and triglyceride (TG) were detected by automatic biochemical analyzer. The pathological changes of liver tissue were observed by HE staining. Results (1) After the model replication,compared with the normal group,the FINS,FPG levels and IR index of the model group were significantly increased (P<0.05). (2) Compared with the normal group,the levels of FINS,FPG and IR index in the model group were significantly increased (P<0.01),the contents of ATP,ADP and AMP in liver tissue were significantly decreased (P<0.01), the content of FFA was significantly increased (P<0.01),and the levels of TC and TG in serum were significantly increased (P<0.05). Liver cells arranged in disorder,fatty degeneration,and there are a large number of lipid droplets. Compared with the model group,the FINS level and IR index of rats in each administration group were significantly decreased (P<0.05, P<0.01), and the FPG level of rats in the Rosiglitazone group was significantly decreased (P<0.05). The contents of ADP and AMP in liver tissue of rats in each administration group were significantly increased (P<0.05,P<0.01),and the contents of ATP in liver tissue of rats in low-,medium- and high dose- groups of Gegen Qinlian Decoction were significantly increased (P<0.05, P<0.01). The content of FFA in liver tissue of rats in Rosiglitazone group and Gegen Qinlian Decoction low- and high- dose groups was significantly decreased (P<0.01). The serum TC level of rats in the low- and high- dose groups of Gegen Qinlian Decoction was significantly decreased (P<0.05, P< 0.01),and the serum TG level of rats in the Rosiglitazone group and the low-dose group of Gegen Qinlian Decoction was significantly decreased (P<0.05, P<0.01). The steatosis of hepatocytes in rats of each administration group was alleviated to varying degrees,and the lipid droplets were reduced,and the pathological damage was improved. Conclusion Gegen Qinlian Decoction may improve liver lipid metabolism disorder and restore lipid and energy balance by regulating energy metabolism and reducing FFA level,thus improving IR.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金项目(82060826);江西省教育厅科学技术研究项目(GJJ2200956);第四批中青年骨干人才计划项目(赣中医药科教字 [2022]6号);江西中医药大学校级科技创新团队发展计划项目(CXTD22007)。