机构地区:[1]四川省中医药科学院四川省中医药转化医学中心,中医药转化医学四川省重点实验室,国家中医药管理局中药质量生物评价重点研究室,四川省道地药材形成原理与品质评价工程研究中心,四川省道地药材系统开发工程技术研究中心,成都610041 [2]四川大学华西药学院,成都610041
出 处:《中药药理与临床》2022年第2期141-146,共6页Pharmacology and Clinics of Chinese Materia Medica
基 金:国家自然科学基金青年科学基金项目(编号:81703820)
摘 要:目的:研究藏药俄色改善KK-Ay小鼠脂代谢紊乱的作用及可能的作用机制。方法:10只C57BL/6J小鼠作为正常对照组,50只KK-Ay模型小鼠按空腹血糖值随机分为模型对照组、阳性对照组(罗格列酮片2.67 mg/kg)和俄色提取物0.75、1.5、3.0 g原生药/kg组,每组10只,连续灌胃给药35 d,末次药后测定小鼠血清游离脂肪酸(FFA)、三酰甘油(TG)、总胆固醇(TC)和肿瘤坏死因子-α(TNF-α)含量;油红O染色法检测肝脏组织中脂质的含量;免疫组化法检测肾周脂肪组织中超氧化物酶体增殖物激活受体-α(PPAR-α)和PPAR-γ蛋白表达;实时定量荧光(PCR)检测Ppar、Tnfa mRNA表达。结果:与正常对照组比较,模型对照组小鼠体质量显著升高,血清FFA、TG、TC、TNF-α含量显著升高(P<0.01),小鼠皮下脂肪系数和腹腔脂肪系数显著升高,小鼠肝脏组织脂滴面积百分比显著升高(P<0.01),小鼠脂肪组织PPAR-α、γ蛋白表达明显降低,肾周脂肪组织Ppar mRNA表达明显下调(P<0.05);与模型对照组比较,俄色提取物1.5、3.0 g/kg组小鼠体质量和皮下脂肪系数明显降低,小鼠肝脏组织脂滴面积百分率明显降低,脂肪组织PPAR-α蛋白明显升高,肾周脂肪组织Ppar mRNA表达明显上调(P<0.05或P<0.01);俄色提取物3.0 g/kg组小鼠血清FFA、TG、TNF-α含量明显降低,肾周脂肪组织Tnfa mRNA表达明显降低(P<0.05或P<0.01);俄色提取物0.75 g/kg组小鼠血清TC含量明显降低、小鼠皮下脂肪系数降低(P<0.05)。结论:藏药俄色可改善KK-Ay小鼠脂质代谢紊乱,其作用机制可能与上调肾周脂肪组织PPARα蛋白表达和PPARγ转录以及减轻炎症反应有关。Objective:To investigate the effects and underlying mechanism of Tibetan medicine Ese on lipid metabolism disorders in KK-Ay mice.Methods:Ten C57 BL/6 J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into a model control group,a rosiglitazone(2.67 mg/kg)group,and low-,medium-,and high-dose Ese extract groups(0.75 g,1.5 g,and 3.0 g/kg crude drug),with 10 mice in each group according to fasting blood glucose levels.The serum levels of free fatty acid(FFA),triglyceride(TG),total cholesterol(TC),and tumor necrosis factor-α(TNF-α)were determined after 35 days of continuous administration by gavage.Lipid content in liver tissues was detected by oil red O staining.The protein expression of peroxisome proliferator-activated receptor-α(PPAR-α)and peroxisome proliferator-activated receptor-γ(PPAR-γ)in perirenal adipose tissues was determined by the immunohistochemical method.The mRNA expression of PPAR and TNF-αwas detected by real-time quantitative PCR.Results:Compared with the normal control group,the model control group showed increased body weight,increased serum content of FFA,TG,TC,and TNF-α(P<0.01),elevated subcutaneous fat and abdominal fat coefficients,increased percentage of lipid droplet expression area in liver tissues(P<0.01),reduced protein expression of PPAR-αand PPAR-γin adipose tissues,and down-regulated PPAR mRNA expression in perirenal adipose tissues(P<0.05).Compared with the model control group,the medium-and high-dose Ese extract groups displayed reduced body weight and subcutaneous fat coefficient(P<0.05),decreased percentage of lipid droplet expression area in liver tissues,increased protein expression of PPAR-αin adipose tissues,and up-regulated expression of PPAR mRNA in perirenal adipose tissues(P<0.01 or P<0.05).In the high-dose Ese extract group,the serum levels of FFA,TG,and TNF-αdecreased and the expression of TNF-αmRNA in perirenal adipose tissues was reduced(P<0.01 or P<0.05).In the low-dose Ese extract group,the serum TC level was red
关 键 词:俄色 自发性2型糖尿病小鼠 脂代谢 超氧化物酶体增殖物激活受体-γ 肿瘤坏死因子-Α
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