氯原酸对db/db小鼠糖脂代谢紊乱的影响及其作用机制

摘要

目的 研究氯原酸(CGA)对自发性肥胖糖尿病db/db小鼠糖脂代谢紊乱的影响及其作用机制.方法 将13只5～6周龄雄性db/db小鼠随机分为db/db-CGA组(n=7)和db/db-CON组(n=6),13只5～6周龄雄性db/m小鼠随机分为db/m-CGA组(n=6)和db/m-CON组(n=7);CGA组均给予80mg/(kg·d)CGA灌胃,CON组均给予等体积PBS灌胃.12周后检测血浆、肝脏、骨骼肌中糖脂生化指标,内脏脂肪组织中脂联素和内脂素含量,肝脏葡萄糖-6-磷酸酶(G-6-Pase)和过氧化物酶体增殖物激活受体-α(PPAR-α)的mRNA水平及其蛋白表达.结果 给予CGA12周后,db/db-CGA组小鼠血浆、肝脏和骨骼肌中三酰甘油含量和空腹血糖均明显低于db/db-CON组(P均＜0.05),肌糖原含量明显高于db/db-CON组(P＜0.05);脂联素水平明显高于db/db-CON组(P＜0.01),低于db/m-CGA组(P＜0.05);内脂素水平明显低于db/db-CON组(P＜0.01),高于db/m-CGA组(P＜0.05);G-6-Pase mRNA表达水平较db/db-CON组明显下降(P＜0.05),PPAR-α mRNA和蛋白表达水平均较db/db-CON组明显升高(P＜0.05).结论 CGA可改善自发性肥胖糖尿病小鼠糖脂代谢紊乱,其机理可能与调节脂肪因子分泌,上调肝脏PPAR-α水平及抑制G-6-Pase表达有关.%Objective To explore the effect of chlorogenic acid on disordered glucose and lipid metabolism in db/db mice and its mechanism. Methods Thirteen 5-6-week-old male db/db mice were randomly divided into db/db-CG A group ( n =7 ) and db/db-CON group ( n =6) , and thirteen 5-6-week-old male db/m mice were randomly divided into db/m-CG A group (n= 6) and db/m-CON group (n= 7 ). Mice in the CGA groups were administrated with CGA 80 mg/( kg · d) by gavage, and mice in the CON groups were administrated with PBS in the same volume by gavage. Twelve weeks later, the level of biomedical parameters in plasma, liver, and skeletal muscle were determined, the concentrations of adiponectin and visfatin in visceral adipose, and the mRNA expression of glucose-6-phosphatase (G-6-Pase) and peroxisome proliferators-activated receptor-α (PPAR-α) as well as the protein level of PPAR-α in liver were detected. Results Twelve weeks after CGA administration, the levels of triglycerides in plasma, liver, and skeletal muscle and the fasting plasma glucose in db/db-CGA group were significantly lower than those in db/db-CON group ( P ＜ 0.05 ). The muscle glycogen level was significantly higher than that in db/db-CON group (P ＜ 0.05 ), and the adiponectin concentration was significantly higher than that in db/db-CON group ( P ＜ 0.01 ) and lower than that in db/m-CGA group (P ＜ 0.05). The visfatin concentration in db/db-CGA group was significantly lower than that in db/db-CON group ( P ＜ 0.01 ) and significantly higher than that in db/m-CGA group ( P ＜ 0.05 ). The mRNA expression level of G-6-Pase was significantly down-regulated in db/db-CGA group when compared with db/db-CON group ( P ＜ 0.05 ). Both the mRNA and the protein expression levels of PPAR-α were significantly up-regulated in db/db-CGA group (P ＜ 0.05 ) compared with in db/db-CON group. Conclusion CGA improves the disordered glucose/lipid metabolism in db/db mice, which is speculated to be related with its role in modulating the adipokines secretion, up-regulating hepatic PPAR-α, and inhibiting G-6-Pase expression.