消渴饮改善ob/ob小鼠胰岛素抵抗的药效学作用及其机制  

Pharmacodynamic Effect and Mechanism of Xiaoke Drink in Ameliorating Insulin Resistance in ob/ob Mice

作　　者：李宝赢 赵保胜 查玉玲 邓秘 牛露娜 李雪菲 朱若维 董宇[3] 荆鲁[1] LI Baoying;ZHAO Baosheng;ZHA Yuling;DENG Mi;NIU Luna;LI Xuefei;ZHU Ruowei;DONG Yu;JING Lu(Eye Hospital,China Academy of Chinese Medical Sciences,Beijing 100040,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院眼科医院,北京100040 [2]北京中医药大学北京中医药研究院,北京100029 [3]中国中医科学院广安门医院,北京100053

出　　处：《中国实验方剂学杂志》2024年第23期254-260,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2019YFC1710101);首都卫生发展科研专项(首发2024-2-4182)。

摘　　要：目的:观察消渴饮对ob/ob小鼠胰岛素抵抗的改善作用,并探析其可能的作用机制。方法:将18只ob/ob小鼠随机分为模型组、消渴饮组(17.68 g·kg^(-1))、阿托伐他汀组(0.01 g·kg^(-1)),每组6只,另设6只C57BL/6小鼠做为正常组。正常组小鼠、模型组小鼠灌胃等量蒸馏水。各组小鼠每周固定时间测定空腹体质量,以及周进食量、周饮水量。干预8周,干预前后测定小鼠空腹血糖(FPG)、糖负荷后2 h血糖(2 hPG)。干预后测算小鼠总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血常规、碱性磷酸酶(ALP),并进行蛋白免疫印迹法(Western blot)检测小鼠肝脏组织泛素特异性蛋白酶20(USP20)、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)蛋白表达,以及胰腺组织苏木素-伊红(HE)染色观察。结果:与模型组比较,消渴饮组ob/ob小鼠体质量明显降低(P<0.05,P<0.01),体质量增长明显下降(P<0.05,P<0.01),周均饮水量、FPG、2 hPG、TC、HOMA-IR水平均明显降低(P<0.05,P<0.01),肝脏组织USP20表达水平明显下降(P<0.05),HMGCR含量与USP20表达存在正相关趋势。同时消渴饮还可以改善ob/ob小鼠胰岛组织形态、促进胰岛功能恢复。结论:消渴饮可以改善ob/ob小鼠胰岛素抵抗,其机制可能与抑制USP20/HMGCR通路表达、逆转胆固醇生物合成过程、降低胆固醇水平有关。Objective:To observe the effect of Xiaoke drink on insulin resistance in ob/ob mice and explore the mechanism.Method:Eighteen ob/ob mice were randomly assigned into model,Xiaoke drink(17.68 g·kg^(-1)),and atorvastatin(0.01 g·kg^(-1))groups(n=6),and six C57BL/6 mice were selected as the normal group.Mice in the normal and model groups were administrated with the same amount of distilled water.Fasting body weight,weekly food intake,and weekly water intake were measured at a fixed time.Fasting plasma glucose(FPG)and 2-hour post-load plasma glucose(2 hPG)were measured before and after 8-week intervention.After intervention,total cholesterol(TC),triglyceride(TG),fasting insulin(FINS),Homeostasis Model Assessment-Insulin Resistance(HOMA-IR),blood routine,and alkaline phosphatase(ALP)were measured.Western blot was employed to determine the expression levels of ubiquitin-specific protease 20(USP20)and 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR)in the liver.The pancreas was stained with hematoxylin-eosin for observation.Result:Compared with the model group,the Xiaoke drink group showed decreased body weight of ob/ob mice(P<0.05,P<0.01),declined growth trend of body weight(P<0.05,P<0.01),reduced weekly average water intake,lowered levels of FPG,2 hPG,TC,and HOMA-IR(P<0.05,P<0.01),and down-regulated expression level of USP20 in the liver(P<0.05).HMGCR content was positively correlated with USP20 expression.In addition,Xiaoke drink promoted the recovery of islet tissue morphology and function in ob/ob mice.Conclusion:Xiaoke drink can ameliorate insulin resistance in ob/ob mice by inhibiting USP20/HMGCR expression,reversing cholesterol biosynthesis process,and reducing cholesterol level.

关 键 词：消渴饮 OB/OB小鼠 胰岛素抵抗 胆固醇 作用机制 

分 类 号：R2-0[医药卫生—中医学] R22R2-031R285.5R587.1