北柴胡多糖对D-半乳糖致衰老模型小鼠的保护作用及其机制

Protective effect of Bupleurum chinense polysaccharide on aging model mice induced by D-galactose and its mechanism

目的:探讨北柴胡多糖(BCP)对D-半乳糖诱导的衰老模型小鼠的保护作用并阐明其作用机制。方法:将25只小鼠随机分为对照组(给予生理盐水)、模型组(给予120 mg·kg^-1 D-半乳糖)、阳性对照组(给予120 mg·kg^-1 D-半乳糖和100 mg·kg^-1 VE)、低剂量BCP组(给予120 mg·kg^-1 D-半乳糖和200 mg·kg^-1 BCP)、高剂量BCP组(给予120mg·kg^-1 D-半乳糖和400 mg·kg^-1 BCP)。对照组小鼠每日腹腔注射生理盐水,其余各组小鼠均腹腔注射D-半乳糖构建小鼠衰老模型。检测各组小鼠体质量、肝脏指数和肾脏指数,检测各组小鼠血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)水平,HE染色检测各组小鼠肝组织形态表现,Western blotting法检测各组小鼠肾组织中p53和p16蛋白表达水平。结果:连续注射D-半乳糖7周后,与对照组比较,模型组小鼠体质量明显降低(P<0.05),肝脏指数和肾脏指数增大(P<0.05),血清SOD和GSH-Px活性降低(P<0.01),MDA水平升高(P<0.01),肾脏组织中p53和p16蛋白表达水平升高(P<0.01),肝细胞水肿明显,肝组织损伤严重。与模型组比较,低和高剂量BCP组小鼠体质量明显升高(P<0.05),肝脏指数和肾脏指数降低(P<0.05),血清SOD和GSH-Px活性升高(P<0.01),MDA水平降低(P<0.01),肾脏组织中p53和p16蛋白表达水平降低(P<0.05或P<0.01),肝细胞形态逐渐趋于正常,肝损伤情况得到缓解。结论:BCP可通过抑制氧化应激及其下游p53和p16信号通路进而抑制D-半乳糖诱导的小鼠衰老。

Objective:To investigate the protective effect of Bupleurum chinense polysaccharide(BCP)on the aging model mice induced by D-galactose,and to elucidate its mechanism.Methods:A total of 25 mice were randomly divide into control group(given saline),model group(given 120 mg·kg-1 D-galactose),positive control group(given 120 mg·kg-1 D-galactose and 100 mg·kg-1 VE),low dose of BCP group(given 120 mg·kg-1 D-galactose and 200 mg·kg-1 BCP),high dose of BCP group(given 120 mg·kg-1 D-galactose and 400 mg·kg-1 BCP).The mice in control group were injected intraperitoneally daily with saline,and the mice in the other groups were injected with D-galactose intraperitoneally to construct the aging models.The body weights,liver indexes,and kidney indexes of the mice in various groups were detected;the serum activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)and the serum levels of malondialdehyde(MDA)of the mice in various groups were detected;HE staining was used to detect the morphology of liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of p53 and p16 proteins in kidney tissue of the mice in various groups.Results:After 7 weeks of continuous injection of D-galactose,compared with control group,the body weight of the mice in model group was significantly decreased(P<0.05),and the liver index and kidney index were increased(P<0.05),the activities of SOD and GSH-Px in serum were decreased(P<0.01),and the level of serum MDA was increased(P<0.01);the expression levels of p53 and p16 proteins in kidney tissue were increased(P<0.01);meanwhile,the hepatocyte edema was obvious,the liver tissue injury was severe.Compared with model group,the body weights of the mice in low and high doses of BCP groups were significantly increased(P<0.05),the liver indexes and kidney indexes were decreased(P<0.05),the activities of SOD and GSH-Px in serum were increased(P<0.01),the levels of serum MDA were decreased(P<0.01),and the expression levels of p53 and p16 proteins in kidney tissue were decreased(P<0.05 or P<0.01);the morphology of liver cells was gradually normalized and the liver injury was alleviated.Conclusion:BCP can inhibit the D-galactose-induced aging in the mice by inhibiting the oxidative stress and its downstream p53 and p16 signaling pathways.