摘要
目的探讨左归降糖清脂方对2型糖尿病合并非酒精性脂肪性肝病MKR鼠内脂素(Visfatin)信号分子的影响。方法8周龄MKR小鼠,按性别、空腹血糖、体质量随机分为空白组、模型组、中药组、阳性药物组;同龄C57/BL/6小鼠作为正常组;每组16只。除正常组、空白组外,其余小鼠高脂饲养8周。中药组予左归降糖清脂方溶液29.6 g/kg,阳性药物组(二甲双胍和辛伐他汀组成,比例为50∶1,给药67.6 mg/kg),其余组予等体积蒸馏水(体积同中药组),灌胃治疗8周。心脏采血处死各组小鼠,采用电化学法检测空腹血糖;常规生化法检测肝功能、血脂;电镜及HE染色观察肝组织形态结构及病理变化;实时荧光定量检测肝脏脂肪组织分泌激素类代谢调节因子Visfatin、视黄醇结合蛋白4(retinol binding protein4,RBP4)的mRNA表达水平;酶联免疫法检测血清炎症因子血清可溶性白细胞介素-2受体(soluble interleukin-2 receptor,SIL-2R)、成纤维细胞生长因子2(fibroblast growth factor2,FGF2)含量的变化。结果与正常组比较,模型组肝细胞内出现明显损伤以及大量脂肪堆积;空腹血糖,谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、血脂含量,RBP4和Visfatin的mRNA表达水平,炎症因子SIL-2R、FGF-2含量均升高(P<0.05或P<0.01)。与模型组比较,中药组与阳性药物组细胞损伤明显改善,空腹血糖浓度降低(P<0.01),ALT、AST、血脂含量明显下降(P<0.01),RBP4和Visfatin的mRNA表达水平降低(P<0.01),炎症因子SIL-2R、FGF-2含量明显下降(P<0.01)。与中药组比较,阳性药物组空腹血糖浓度降低(P<0.05),其余指标无差异。结论左归降糖清脂方可能通过改善肝功能、降低血脂、降低肝组织Visfatin及RBP4的mRNA表达水平、降低血清炎症因子SIL-2R及FGF-2的含量,从而改善2型糖尿病合并非酒精性脂肪性肝病肝脏的病理损伤。
Objective To investigate the effects of Zuogui Jiangtang Qingzhi Formula(ZGJTQZF)on the signaling molecules of Visfatin in MKR mice with type 2 diabetes complicated with non-alcoholic fatty liver disease.Methods Eight-week-old MKR mice were randomly divided into blank group,model group,Chinese medicine(ZGJTQZF)group and positive drug group according to gender,fasting blood glucose and body weight.C57/BL/6 mice of the same age were set as normal group.Sixteen rats were included in each group.Except for normal group and blank group,the other mice were fed with high fat diets for 8 weeks.The Chinese medicine group was given ZGJTQZF(29.6 g/kg),the positive drug group was given metformin and simvastatin(50∶1,67.6 mg/kg),and the other groups were given equal volume of distilled water(the same volume of the Chinese medicine group)for 8 weeks.The mice in each group were sacrificed by cardiac blood collection,and fasting blood glucose was measured by electrochemical method.Liver function and blood lipid were determined by routine biochemical method.The morphological structure and pathological changes of liver tissue were observed by electron microscope and HE staining.The mRNA expression levels of Visfatin and retinol binding protein 4(RBP4)in liver adipose tissue were examined by real-time fluorescence quantitative detection.The levels of serum soluble interleukin-2 receptor(SIL-2R)and fibroblast growth factor 2(FGF2)were checked by enzyme-linked immunosorbent assay.Results Compared with the normal group,the liver cells in model group showed obvious damage and a large amount of accumulated fat.Fasting blood glucose,alanine transaminase(ALT)、aspartate aminotransferase(AST),blood lipids,RBP4 and Visfatin mRNA expression levels,inflammatory factors SIL-2R,FGF-2 content all increased(P<0.05 or P<0.01);compared with model group,the cell damage in the positive drug group and Chinese medicine group was significantly improved,fasting blood glucose concentration decreased(P<0.01);ALT,AST and blood lipids decreased significantly(P<0.01),RBP4 and Visfatin mRNA expression levels decreased(P<0.01),and the content of inflammatory factors SIL-2R,FGF-2 decreased significantly(P<0.01).Compared with the Chinese medicine group,the fasting blood glucose concentration in the positive drug group decreased(P<0.05),and there was no statistical difference in other indicators.Conclusion ZGJTQZF may alleviate the pathological damage of liver in MKR mice with type 2 diabetes complicated with non-alcoholic fatty liver disease by improving liver function,reducing blood lipids,reducing the mRNA expression levels of visfatin and RBP4 in liver tissue,and down-regulating the content of serum inflammatory factors SIL-2R and FGF-2.
作者
勾阳阳
杨娇娇
向琴
喻嵘
陈聪
GOU Yangyang;YANG Jiaojiao;XIANG Qin;YU Rong;CHEN Cong(Guizhou University of Chinese Medicine,Guiyang,Guizhou 550025,China;Hunan University ofChinese Medicine,Changsha,Hunan 410208,China)
出处
《湖南中医药大学学报》
CAS
2023年第4期585-590,共6页
Journal of Hunan University of Chinese Medicine
基金
国家自然科学基金项目(81860818,82004185)
贵州省科学技术厅科技基金(黔科合基础-ZK[2021]一般501)
贵州省中医药管理局中医药、民族医药科学技术研究专项课题(QZYY-2022-010)
2021年贵州省卫生健康委科学技术基金
贵州中医药大学糖脂代谢病研究中心资助。
