23-乙酰泽泻醇B对肥胖模型小鼠糖脂代谢紊乱的改善作用
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篇名: 23-乙酰泽泻醇B对肥胖模型小鼠糖脂代谢紊乱的改善作用
TITLE:
摘要: 目的:研究23-乙酰泽泻醇B对肥胖模型小鼠糖脂代谢紊乱的改善作用及机制。方法:小鼠给予高脂饲料10周以复制肥胖模型。将造模成功的小鼠随机分为模型组、奥利司他组(阳性对照,15.6mg/kg)和23-乙酰泽泻醇B低、中、高剂量组(7.5、15、30mg/kg),每组10只;另设置喂养普通饲料的小鼠10只为正常组。正常组和模型组小鼠灌胃水,给药组小鼠灌胃相应药物,灌胃体积均为20mL/kg,每天1次,连续4周。末次给药后,测定小鼠的体质量、腰围和全身脂肪、肌肉和体液质量;测定小鼠血清中血脂指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)]和血糖水平;采用酶联免疫吸附法测定肝组织中过氧化物酶体增殖剂激活受体γ(PPAR-γ)、核因子κB(NF-κB)、白细胞介素6(IL-6)水平和血清中肿瘤坏死因子α(TNF-α)水平;采用苏木精-伊红染色法观察小鼠脂肪和肝组织的病理变化。结果:与正常组比较,模型组小鼠体质量、腰围、全身脂肪和体液质量均显著增加(P<0.01);血清中TC、TG、HDL-C、血糖、TNF-α水平和肝组织中PPAR-γ、NF-κB、IL-6水平均显著升高(P<0.05或P<0.01);脂肪细胞结构破裂、体积增大,伴有炎性细胞浸润;大量肝细胞水肿,细胞浆疏松淡染,伴有脂肪变性。与模型组比较,23-乙酰泽泻醇B各剂量组小鼠体质量、全身脂肪和体液质量以及血清中TG、TNF-α水平均显著降低(P<0.01);23-乙酰泽泻醇B中、高剂量组小鼠血清中TC、血糖和肝组织中IL-6均显著降低(P<0.05或P<0.01),肝组织中PPAR-γ水平均显著升高(P<0.05或P<0.01);23-乙酰泽泻醇B高剂量组小鼠腰围和肝组织中NF-κB显著减少或降低(P<0.01);23-乙酰泽泻醇B中剂量组小鼠血清中HDL-C水平显著降低(P<0.01);脂肪细胞排列紧密、体积较小;肝细胞轻中度肿胀,少量细胞浆疏松淡染或呈空泡状,少量肝细胞伴脂肪变性和炎性细胞小灶性浸润。结论:23-乙酰泽泻醇B可改善肥胖模型小鼠的糖脂代谢紊乱,其作用机制可能与调节肝组织中PPAR-γ、NF-κB、IL-6水平和血清中TNF-α水平有关。
ABSTRACT: OBJECTIVE:To st udy the improvement effects and its mechan ism of alisol B 23-acetate on glycolipid metabolism disorder in obesity model mice. METHODS :The mice was given high-fat diet for 10 weeks to induce obesity model. Model mice were randomly divided into model group ,orlistat group (positive control ,15.6 mg/kg), alisol B 23-acetate low-dose , medium-dose and high-dose groups (7.5,15,30 mg/kg),with 10 mice in each group. Another 10 mice fed with normal diet were set as normal group. The mice in normal group and model group were given water intragastrically ,and administration groups were given the corresponding drugs intragastrically ,with the volume of 20 mL/kg,once a day ,for consecutive 4 weeks. After last medication,body weight ,waist circumference ,body fat ,muscle and body fluid mass were measured ;the serum levels of blood lipids indicators (TC,TG,HDL-C,LDL-C)and blood glucose were determined. The levels of PPAR-γ,NF-κB and IL-6 in liver tissue as well as serum level of TNF-α were determined by ELISA. The pathomorphological changes of visceral fat and liver tissue in mice were observed by HE staining. RESULTS :Compared with normal group ,body weight ,waist circumference ,body fat and body fluid mass were significantly increased in model group (P<0.01);serum levels of TC ,TG,HDL-C,blood glucose and TNF-α,the levels of PPAR-γ,NF-κB and IL-6 in liver tissue were increased significantly (P<0.05 or P<0.01);the structure of adipocytes was ruptured ,the volume of adipocytes was increased ,accompanied by inflammatory cell infiltration ;a large number of liver cells were edema ,and cytoplasm was loose and light stained,accompanied by fatty degeneration. Compared with model group ,the body weight ,body fat and body fluid mass as well as serum le vels of TG and TNF-α in alisol B 23-acetate groups were significantly reduced (P<0.01);the levels of TC and blood glucose in serum ,IL-6 in liver tissue were significantly decreased in alisol B 23-acetate medium-dose and high-dose groups (P<0.05 or P<0.01),and the level of PPAR-γ in liver tissue was increased significantly(P<0.05 or P<0.01); the waist circumference and NF-κB levels in liver tissue in alisol B 23-acetate high-dose group were decreased significantly (P< 0.01);serum level of HDL-C in alisol B 23-acetate medium-dose group were decreased significantly (P<0.01);the adipocytes were closely arranged and small in size ;the hepatocytes were mild to moderate swelling ,a small amount of cytoplasm was loose , light stained or vacuolated ,and a small number of hepatocytes were accompanied by steatosis and small focal infiltration of inflammatory cells. CONCLUSIONS :Alisol B 23-acetate can improve the disorder of glucose and lipid metabolism in obesity model mice ,and its mechanism may be related to the regulation of PPAR-γ,NF-κB,IL-6 levels in liver tissue and TNF-α levels in serum.
期刊: 2021年第32卷第09期
作者: 吴珍,魏瑶,杨玉姣,徐贵涛,谢颖,胡旭光
AUTHORS:
关键字: 23-乙酰泽泻醇B;肥胖;糖脂代谢紊乱;小鼠
KEYWORDS: Alisol B 23-acetate;Obesity;Glucose and lipid metabolism disorder ;Mice
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