摘要
目的探讨西格列汀对糖尿病前期KKAy小鼠各代谢指标及脂肪因子趋化素水平的影响及其可能的机制。方法将30只KKAy小鼠随机分为普通饲料喂养组(NC组,n=10)与高脂饲料喂养组(HF组,n=20)。8周后将高脂饲料喂养的KKAy小鼠随机分为高脂对照组(HFC组,n=10)与西格列汀干预组(SP组,n=10)。HFC组灌胃给予2 ml生理盐水作为空白对照;SP组给予盐酸西格列汀。观察各组小鼠生理指标。采用酶联免疫吸附法分别测定各组小鼠胰岛素、趋化素、脂联素水平。采用蛋白免疫印迹法检测小鼠网膜、皮下脂肪和肝趋化素蛋白水平。结果干预前,HFC组与SP组小鼠的体质量、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMO-IR)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均显著高于NC组,差异有统计学意义(P<0.05);HFC组与SP组各指标比较,差异无统计学意义(P>0.05)。干预后,SP组FBG、HOMO-IR、TC、TG及LDL-C水平均显著低于HFC组,FINS、胰岛β细胞功能指数(HOMO-β)显著高于HFC组,差异有统计学意义(P<0.05)。干预前,HFC组及SP组趋化素水平均显著高于NC组,脂联素水平均显著低于NC组,差异有统计学意义(P<0.05)。干预后,SP组血清趋化素水平显著低于HFC组,脂联素水平显著高于HFC组,差异有统计学意义(P<0.05)。与NC组比较,HFC组小鼠的网膜脂肪和皮下脂肪趋化素蛋白的表达水平均显著升高,差异有统计学意义(P<0.05)。与HFC组比较,SP组小鼠的网膜脂肪和皮下脂肪中趋化素的蛋白表达水平均显著降低,差异有统计学意义(P<0.05)。多元线性回归分析结果显示,TG、FINS是趋化素表达水平的主要影响因素(P<0.05)。相关性分析结果显示,血清中趋化素的水平与网膜脂肪中该蛋白的表达量呈正相关(r=0.759,95%可信区间0.403~0.927,P<0.05)。结论西格列汀可能通过降低血清、脂肪组织中趋化素水平,改善血清学各代谢指标,改善胰岛素抵抗、恢复胰岛功能,避免糖尿病的发生发展。
Objective To investigate the effect of sitagliptin on metabolic parameters and chemerin levels of prediabetes KKAy mice and its possible mechanism.Methods Thirty KKAy mice were randomly divided into the normal feed group(NC group,n=10)and the high-fat feed group(HF group,n=20).After 8 weeks,KKAy mice with high-fat diet were randomly divided into the high-fat control group(HFC group,n=10)and sitagliptin intervention group(SP group,n=10).In the HFC group,2 ml normal saline was given by gavage as a blank control.SP group was given sitagliptin hydrochloride.The physiological indexes of each group were observed.The levels of insulin,chemerin and adiposectin in KKAy mice were determined by enzyme-linked immunosorbent assay.The levels of omentum,subcutaneous fat and hepatic chemerin proteins in KKAy mice were detected by Western blot.Results Before intervention,body mass,fasting blood-glucose(FBG),fasting insulin(FINS),insulin resistance index(HOMO-IR),total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)of KKAy mice in HFC group and SP group were significantly higher than that in NC group,with statistically significant differences(P<0.05).There was no significant difference between HFC group and SP group(P>0.05).After intervention,FBG,HOMO-IR,TC,TG and LDL-C levels in the SP group were significantly lower than those in the HFC group,and the FINS and HOMO-β levels were significantly higher than those in the HFC group(P<0.05).Before the intervention,the levels of chemerin in both the HFC group and the SP group were significantly higher than that in the NC group,and the levels of adiponectin were significantly lower than that in the NC group(P<0.05).After intervention,the level of chemerin in SP group was significantly lower than that in HFC group,and the levels of adiponectin were significantly higher than that in the HFC group(P<0.05).Compared with NC group,the expression levels of omental fat and subcutaneous fat chemerin protein in KKAy mice in HFC group were significantly increased(P<0.05).Compared with the HFC group,the protein expression levels of chemerin in omental fat and subcutaneous fat of KKAy mice in SP group were significantly reduced(P<0.05).The results of multiple linear regression analysis showed that TG and FINS were the main factors affecting the expression level of chemerin(P<0.05).The results of correlation analysis showed that the level of chemerin in serum was positively correlated with the expression of this protein in omental fat(r=0.759,95%CI 0.403~0.927,P<0.05).Conclusion Sitagliptin may reduce the levels of chemerin in serum and adipose tissue,improve the metabolic indexes of serology,improve insulin resistance,restore pancreatic islet function,and avoid the occurrence and development of diabetes.
作者
李萍
梁琳琅
王宇
侯达
杨昕
杨博
刘文源
王彤
LI Ping;LIANG Lin-liang;WANG Yu;HOU Da;YANG Xin;YANG Bo;LIU Wen-yuan;WANG Tong(Department of Rheumatology and Immunology,General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Endocrinology,General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Diagnostic Radiology,General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Biology,The Northeast University,Shenyang 110000,China)
出处
《临床军医杂志》
CAS
2020年第4期376-379,382,共5页
Clinical Journal of Medical Officers
基金
辽宁省自然科学基金(201602776)。
