首页|葛根芩连汤对胰岛素抵抗大鼠肝脏能量代谢及游离脂肪酸的影响

葛根芩连汤对胰岛素抵抗大鼠肝脏能量代谢及游离脂肪酸的影响

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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.
Effects of Gegen Qinlian Decoction on Liver Energy Metabolism and Free Fatty Acids in Insulin Resistant Rats
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.

Gegen Qinlian Decoctioninsulin resistanceenergy metabolismfree fatty acidslipid metabolismrats

张文彤、姜丽、房文洁、张启云、李冰涛、黄丽萍、徐国良

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江西中医药大学中医基础理论分化发展研究中心,江西省中医病因生物学重点实验室,江西 南昌 330004

江西省中药药理学重点实验室,江西 南昌 330004

葛根芩连汤 胰岛素抵抗 能量代谢 游离脂肪酸 脂质代谢 大鼠

国家自然科学基金江西省教育厅科学技术研究项目中青年骨干人才计划(第四批)江西中医药大学校级科技创新团队发展计划

82060826GJJ2200956赣中医药科教字[2022]6号CXTD22007

2024

中药新药与临床药理
广州中医药大学

中药新药与临床药理

CSTPCD北大核心
影响因子:0.908
ISSN:1003-9783
年,卷(期):2024.35(5)
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