熊果酸改善自然衰老大鼠糖脂代谢紊乱与自噬能力的研究

Ursolic acid improves age-related glycolipid metabolism disorder and autophagy in rats

为研究熊果酸对自然衰老大鼠糖脂代谢紊乱和自噬功能影响。实验取22月龄SD雄性大鼠25只,随机分为3组,即老年模型组(n=9),熊果酸低剂量组(UA-L):灌胃给予熊果酸10 mg/kg(n=8),熊果酸高剂量组(UA-H):灌胃给予熊果酸50 mg/kg(n=8);另取8只3月龄SD青年大鼠作为青年对照组,均给予常规正常饮食饮水并记录摄食量和体重变化。用酶法和ELISA法检测血浆葡萄糖、甘油三酯和胰岛素并计算HOMA-IR指数,测定肝脏甘油三酯;油红"O"染色观察肝脏脂质沉积情况;Western blot法检测肝脏自噬相关蛋白及线粒体质量相关蛋白的表达。结果显示熊果酸(50 mg/kg)并不影响大鼠食物摄入量、体质量,但是逆转了老年大鼠血浆甘油三酯、胰岛素和HOMA-IR的升高,降低了肝质量、肝脏TG含量、改善了肝脏脂质沉积(P<0.05),与此同时老年大鼠肝脏自噬相关蛋白LC3B/3A,Beclin1和线粒体质量控制蛋白PGC-1α,Drp1的表达显著升高,但对P62、Pink1的表达无影响。根据以上实验结果推测熊果酸可以提高胰岛素敏感性,改善老年大鼠脂肪肝,增强肝细胞自噬,提高线粒体质量。

This study aims to investigate the effect of ursolic acid ( UA) on glycolipid metabolism disorder and hepatic auto- phagy in naturally ageing rats. Twenty-five male aging rats were divided randomly into three groups: the natural aging rat group ( Aging,n = 9),the aging rats supplemented with ursolic acid at 10 mg /kg ( UA-L,n = 8) and 50 mg /kg ( UA-H,n = 8) for 7 weeks. Eight young rats were randomly selected as the young normal group ( Young,n = 8). Enzymatical method and ELISA were used for the examination of plasma glucose,triglycerides,insulin concentrations and HOMA-IR index was calculated;Liver triglycerides were measured by enzymatical method;Liver lipid deposition was observed by Oil Red " O" staining;The autophagy-related proteins and mitochondrial quality proteins were analysed by Western blot. Results showed that treatment with UA ( 50 mg /kg,once daily,by oral gavage) could attenuate age-associated high plasma TG and insulin concentration un- der fasting conditions as well as suppress the increase in the HOMA-IR index,which suggests there is an improvement of sys- temic insulin sensitivity. Moreover,liver weight and hepatic triglyceride content were also decreased. Attenuation of the in- creased Oil Red O staining area was evident on histological examination of liver in UA ( 50 mg /kg)-treated rats. Importantly, UA ( 50 mg /kg) administration reversed the decreased expressions of autophagy-related proteins LC3B/3A,Beclin1 and mito- chondrial quality proteins PGC-1α,Drp1 in aging rats,although P62,Pink1 remained unchanged. The results suggest that UA may attenuate systematic insulin resistance and hepatic lipid deposition,enhance hepatic autophagy,improve mitochondrial quality in aging rats.