中药降脂复方对新西兰白兔胆固醇-胆汁酸代谢的调节  

Study on the Regulation of Chinese Medicinal Lipid-Lowering Compound on Cholesterol-Bile Acid Metabolism in New Zealand White Rabbits

作　　者：陈瑜[1] 邱冬妮[1] 孙思佳 卓家隆 廖阳勃 孙旭[1] 毛奇琦[1] 丁伟群[1] 邱志兵[1] 邵雷[1] CHEN Yu;QIU Dong-ni;SUN Si-jia;ZHUO Jia-long;LIAO Yang-bo;SUN Xu;MAO Qi-qi;DING Wei-qun;QIU Zhi-bing;SHAO Lei(Huashan Hospital Affiliated to Fudan University,Shanghai,China,200040)

机构地区：[1]复旦大学附属华山医院,上海200040

出　　处：《河南中医》2023年第1期33-38,共6页Henan Traditional Chinese Medicine

基　　金：国家科技部重大专项项目(2018ZX10302206-005-007);上海申康医院发展中心《促进市级医院临床技能与临床创新三年行动计划》重大临床研究项目(SHDC2020CR1037B)。

摘　　要：目的:探讨中药降脂复方对新西兰白兔胆固醇-胆汁酸代谢的调节机制。方法:采用随机数字表法将60只新西兰白兔分为对照组、模型组、中药降脂复方低剂量组和中药降脂复方高剂量组,每组15只。除对照组外,其余组新西兰白兔给予高胆固醇饮食,同时给予相应药物进行灌胃,每天1次,连续4周。ELISA法检测肝脏胆固醇7α羟化酶(cholesterol 7α hydroxylase, CYP7A1)的水平;酶水解法测定血清总胆固醇(total cholesterol, TC)、总胆红素(total bilirubin, TBIL)的水平;酶循环法测定血清总胆汁酸(total bile acid, TBA)水平;HE染色检测肝脏病理变化;RT-PCR检测小异源二聚体伴侣(small heterodimer partner, SHP)、胆盐输出泵(bile salt export pump, BSEP)和三磷酸腺苷结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1) mRNA相对表达量。结果:与对照组相比,模型组TC、TBIL水平及SHP mRNA、BSEP mRNA、ABCA1 mRNA相对表达量升高,TBA水平及CYP7A1活性降低;与模型组相比,中药降脂复方组TBA水平及CYP7A1活性升高,TC、TBIL水平及SHP mRNA、BSEP mRNA、ABCA1 mRNA相对表达量降低,且呈剂量依赖性,差异均具有统计学意义(P<0.05)。HE染色显示,模型组新西兰白兔肝细胞肿大,有炎性细胞浸润;给予中药降脂复方后,各组新西兰白兔肝脏病理改变有所改善。结论:中药降脂复方能有效调节新西兰白兔胆固醇-胆汁酸代谢,其作用机制可能与调控SHP、BSEP及ABCA1表达有关。Objective: To study on the regulation of Chinese Medicinal Lipid-Lowering Compound(CMLLC) on cholesterol-bile Acid metabolism in New Zealand white rabbits.Methods: A total of 60 New Zealand white rabbits were randomly divided into the control group, the model group, the low-dose group of CMLLC and the high-dose group of CMLLC,with 15 rats in each group.Except the control group, the rats in other groups were given a high cholesterol diet, and corresponding drugs were given by gavage, once a day for 4 weeks.The level of cholesterol 7α hydroxylase( CYP7A1) was detected by ELISA.The levels of total cholesterol(TC) and total bilirubin(TBIL) in serum were measured by enzymatic hydrolysis.The level of serum total bile acid(TBA) was measured by enzyme circulation method.The pathological changes of liver was detected by HE staining.RT-PCR was used to detect the relative expressions of small heterodimer partner(SHP),bile salt export pump(BSEP) and ATP-binding cassette transporter A1(ABCA1) mRNA.Results: Compared with the control group, the levels of TC and TBIL,the relative expressions of SHP mRNA,BSEP mRNA and ABCA1 mRNA in the model group increased, while the levels of TBA and CYP7A1 activity decreased.Compared with the model group, the level of TBA and the activity of CYP7A1 in the CMLLC groups increased, while the levels of TC and TBIL,the relative expressions of SHP mRNA,BSEP mRNA,ABCA1 mRNA decreased in a dose-dependent manner, and all the differences were statistically significant(P<0.05).HE staining showed that the hepatocytes in the model group were swollen with inflammatory cell infiltration;The liver pathological changes of rats in each group were improved after the treatment of CMLLC.Conclusion: CMLLC can effectively regulate cholesterol bile acid metabolism in New Zealand white rabbits, which may be related to regulating the expressions of SHP,BSEP and ABCA1.

关 键 词：中药降脂复方 胆固醇代谢 胆汁酸代谢 新西兰白兔 

分 类 号：R285.5[医药卫生—中药学]