复方贞术调脂方调节肠道糖吸收功能伴糖代谢改善的机制  

FTZ Improves Intestinal Function in aP2-SREBP1c Lipoatrophic Model Mice

作　　者：余玉英 吴雅韵 王露莎 吴琪 陈远云 韦世杰 荣向路 郭姣 YU Yuying;WU Yayun;WANG Lusha;WU Qi;CHEN Yuanyun;WEI Shijie;RONG Xianglu;GUO Jiao(Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine,Guangzhou 510006 Guangdong,China;Guangdong TCM Key Laboratory Against Metabolic Diseases Institute of Chinese Medicinal Sciences,Guangzhou 510006 Guangdong,China;Joint Laboratory between Guangdong and HongKong on Metabolic Diseases,Guangzhou 510006 Guangdong,China)

机构地区：[1]广东省代谢病中西医结合研究中心,广东广州510006 [2]广东省代谢性疾病中医药防治重点实验室,广东广州510006 [3]教育部糖脂代谢病粤港澳联合实验室,广东广州510006

出　　处：《中药新药与临床药理》2019年第5期509-515,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金重点项目(81530102,81830113);广东省科技厅实验室建设项目(2017B030314064);广东省自然科学基金重点项目(2015A03031103);广东省高等学校高层次人才项目(51439003)

摘　　要：目的研究复方贞术调脂方(FTZ)对脂肪萎缩模型小鼠(aP2-SREBP1c转基因小鼠)肠道功能的影响,探讨FTZ改善糖脂代谢病的作用机制。方法aP2-SREBP1c小鼠随机分为模型组(T),二甲双脈组(Met,250mg·kg^-1),FTZ高(FH)、中(FM)、低(FL)剂量组(2.4、1.2、0.6g·-kg^-1),并以同窝野生型小鼠为对照组(W),每组6只;连续灌胃给药16周,每天1次,对照组及模型组给予等量蒸馏水每日记录小鼠体质量变化;给药12周末,小鼠眼眶取血测定葡萄糖、甘油三酯和总胆固醇水平;给药16周末,取小鼠肠管量取长度、称定肝脏质量并计算肝体比系数;苏木素-伊红染色(HE)观察十二指肠、空肠、回肠形态变化;实时荧光定量PCR法(Real-time PCR)检测空肠钠-葡萄糖共转运体l(Slc5a1)、葡萄糖转运蛋白l(Slc2a1)、葡萄糖转运蛋白2(Slc2a2)、葡萄糖转运蛋白5(Slc2a5)、血清和糖皮质激素调节激酶1(Sgk1)等糖转运相关基因mRNA水平,以及白细胞介素15(IL15)、BCL2样蛋白(BCL2L1)、髓细胞白血病1基因(MCL-1)、B淋巴细胞瘤/白血病因子3(BCL3)等抗凋亡相关基因mRNA水平;免疫荧光法检测空肠组织中葡萄糖转运蛋白2(Glucose transporter2,GLUT2)蛋白表达:结果与模型组比较,FTZ中剂量组的体质量明显下降(P<0.05).FTZ中、高剂量组的血糖、总胆固醇明显下降(P<0.05),甘油三酯明显升高(P<0.05),对肝体比系数的影响不明显(P>0.05);FTZ高剂量组的肠管长度明显缩短(P<0.05),FTZ中剂量组的近端空肠绒毛长度明显缩短(P<0.05);FTZ中剂量组小鼠空肠组织的Slc2a2 mRNA水平显著升高、GLUT2蛋白表达显著增加(P<0.05)。结论FTZ可恢复aP2-SREBP1c脂肪萎缩模型小鼠肠管长度,缩短空肠组织肠绒毛长度,增加空肠组织Slc2a2(GLUT2)转录水平并增加空肠肠绒毛上皮细胞GLUT2表达,从而恢复小鼠肠道糖吸收功能,这可能是FTZ调节糖代谢平衡的机制之一。Objective To investigate the therapeutic effect of FTZ on aP2-SREBP1c transgene mice and its possible pathways.Methods Animals were randomly divided into 6 groups as follows: control group,model group Metformin group(250 mg·kg^-1),FTZ high(2.4 g·kg^-1),middle(1.2 g·kg^-1),and low dose(0.6 g·kg^-1)groups;the normal group and model group were given distilled water,and the rest of the groups were prophylactic given drugs for 16 weeks.The blood glucose,triglyceride (TG),total cholesterol (TC) were measured at the 12th week.At the end of the experiment,the basal body weight change,intestinal length of each group were measured and macroscopic appearances of duodenum,jejunum and ileum were observed.The mRNA levels of glucose transporter genes of sodium-glucose cotransporter 1 (Slc5a1),glucose transporter protein type 1 (Slc2a1),glucose transporter protein type 2 (Slc2a2),glucose transporter protein type 5 (Slc2a5),serum and glucocorticoid-regulated kinase 1 (Sgk1) and anti-apoptotic genes of interleukin 15 (IL15),BCL2 like 1 (BCL2L1),myeloid cell leukemia sequence 1 (MCL-1),B cell CLL/lymphoma 3 (BCL3) were detected by Real-time quantitative PCR (RT-qPCR) and the protein expression of glucose transporter 2 (GLUT2)in jejunum tissue was observed by immunofluorescence.Results Compared with the model group,the body mass of mice in FTZ middle dose group was decreased (P < 0.05).FTZ middle and high doses significantly reduced the blood glucose and TC in aP2-SREBP1c transgene mice (P < 0.05),and increased the TG (P < 0.05) in these mice.The intestinal lengths of ETZ high dose group mice were shortened (P < 0.05);the length of intestinal villi in jejunum tissue in FTZ middle dose group (2.4 g·kg^-1) was shortened (P < 0.05).FTZ middle dose up-regulated the Slc2a2 mRNA level and GLUT2 protein level in jejunal tissue (P < 0.05).Conclusion FTZ can improve the intestinal function in aP2-SREBP1c lipoatrophic model mice,which may be a potential mechanism for its improvement of metabolic disorders.

关 键 词：复方贞术调脂方 脂肪萎缩 糖转运 葡萄糖转运蛋白2 肠绒毛 

分 类 号：R285.5[医药卫生—中药学]