摘要
目的:研究虎杖苷对非酒精性脂肪肝的影响及相关分子机制。方法:将健康的42只雄性SD大鼠随机分为正常组(A组)、模型组(B组)和3种不同剂量的虎杖苷组(C1、C2、C3组),模型组和虎杖苷组给予高脂饲料喂养8周,造模成功后,A组和B组给予生理盐水灌胃,C1、C2、C3组分别给予50、100和200mg/(kg·d)的虎杖苷混悬液灌胃。HE染色后观察病理学改变;测定大鼠空腹血糖和胰岛素,并计算胰岛素抵抗指数和胰岛素敏感指数;测定谷胱甘肽-S-转移酶、超氧化物歧化酶及丙二醛含量;实时定量PCR检测炎性因子肿瘤坏死因子-α(TNF-α)和IL-6表达水平;Westernblot方法检测PPAR-α、LXR-α、SREBP-1c蛋白的表达。结果:与A组比较,B组SOD和GST含量均显著性降低,而MDA显著性升高;TNF-α、IL-6mRNA表达均显著性增加;FBG、FNS及IR显著性升高,而ISI显著性降低。与B组比较,虎杖苷各剂量组中SOD和GST含量显著性升高,而MDA显著性降低;C2及C3组TNF-α表达显著性降低,C1、C2及C3组IL-6表达显著性降低;C2及C3组FBG、FNS及IR显著性降低,而ISI显著性升高。Westernblot结果表明B组较A组PPAR-α蛋白表达显著性降低,LXR-α、SREBP-1c蛋白表达显著性增加;与B组比较,C2和C3组LXR-α、SREBP-1c表达显著性下调,而PPAR-α蛋白无明显变化。结论:虎杖苷可能是通过抗氧化作用,抑制脂质过氧化,抑制机体炎症反应,降低胰岛素抵抗,下调脂质合成因子SREBP-1c和LXR-α蛋白的表达,减少脂质合成等关键途径来治疗NAFLD。
Objective: To study the effects of polydatin on nonalcoholic fatty liver and related molecular mechanisms. Methods: 42 healthy male Sprague-Dawley rats were randomly divided into normal group(A),model group(B),and 3 different doses of polydatin group(C1,C2,C3).Model group and polydatin group were given high-fat diet.After 8 weeks of feeding,the rats in groups A and B were given intragastric administration of gavage,and C1,C2 and C3 were given 50,100 and 200 mg/(kg·d) of polydatin suspensions,respectively.The pathological changes were observed after HE staining;fasting blood glucose and insulin were measured;insulin resistance index and insulin sensitivity index were calculated;and the contents of glutathione-S-transferase,superoxide dismutase and malondialdehyde were measured.Real-time quantitative PCR was used to detect the expression of TNF-α and IL-6;Western blot was used to detect the expression of PPAR-α,LXR-α and SREBP-1c. Results: Compared with the group A,SOD and GST levels in the group B were significantly decreased,while MDA significantly increased;TNF-α,IL-6 mRNA expression were significantly increased;FBG,FNS and IR were significantly increased,and ISI significantly reduced.Compared with the group B,the content of SOD and GST in each dose group of polydatin increased significantly,while that of MDA significantly decreased;the expression of TNF-α decreased significantly in groups C2 and C3.The expression of IL-6 was significantly decreased in groups C1,C2,and C3;the FBG,FNS and IR of groups C2 and C3 were significantly decreased,whereas the ISI was significantly increased.Western blot results showed that the expression of PPAR-α protein in group B was significantly lower than that in group A,and the expression of LXR-α and SREBP-1c protein was significantly increased.Compared with the group B,the expression of LXR-α and SREBP-1c was significantly down-regulated,while there was no significant change in PPAR-α protein. Conclusion: Polydatin may be used to treat NAFLD through antioxidation,inhibition of lipid peroxidation,inhibition of body inflammatory response,reduction of insulin resistance,down-regulation of lipid synthesis factors SREBP-1c and LXR-α protein expression,and reduction of lipid synthesis.
作者
刘皎皎
戴玲
董璐
何瑾瑜
李瀚旻
LIU Jiao-Jiao;DAI Ling;DONG Lu;HE Jin-Yu;LI Han-Min(ShanxiProvince Traditional Chinese Medicine Hospital,Xi'an 710003,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2019年第10期1188-1192,共5页
Chinese Journal of Immunology
基金
2015年度国家中医临床研究基地业务建设第二批科研专项(JDZX2015172)
陕西省中医管理局中医药科研课题(LCPT010)
陕西省重点研发计划项目(2017SF-339)资助
关键词
虎杖苷
非酒精性脂肪肝
氧化应激
炎症反应
胰岛素抵抗
Polydatin
Nonalcoholic fatty liver disease
Oxidativestress
Inflammation
Insulin resistance
作者简介
刘皎皎,女,博士,主治医师,主要从事中医药防治肝病方面的研究,E-mail:pingguo21990@163.com;通讯作者:李瀚旻,E-mail:lihanmin69@126.com。
