引用本文:罗福祥1,马福昌1,艾西木江·热甫卡提1,阿不都吉力力·阿布都艾尼1,窦勤1,尤力都孜·买买提1,高莉2,库尔班尼沙·麦提卡思木1.蒺藜生药粉及其水提取物的肝毒性作用机制研究[J].世界中医药,2023,(20):. |
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蒺藜生药粉及其水提取物的肝毒性作用机制研究 |
Hepatotoxic Effects and Mechanisms of Tribuli Fructus Powder and Aqueous Extract |
投稿时间:2022-02-23 |
DOI:10.3969/j.issn.1673-7202.2023.20.006 |
中文关键词: 蒺藜 蒺藜生药粉 蒺藜水提物 肝脏 肝系数 肝毒性 机制 血液生化学 |
English Keywords:Tribuli Fructus Tribuli Fructus powder Aqueous extract of Tribuli Fructus Liver Liver index Hepatotoxicity Mechanism Blood biochemistry |
基金项目:国家科技重大专项(2017ZX09301045);新疆维吾尔自治区自然科学基金面上项目(2020D01A105) |
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中文摘要: |
目的:探讨蒺藜生药粉及其水提取物的肝毒性作用机制。方法:蒺藜生药粉、蒺藜水提取物经口给予SD大鼠1个月。选取健康大鼠140只,雌雄各半,随机分为正常对照组,蒺藜粉低、中、高剂量组,蒺藜水提物低、中、高剂量组。检测大鼠血清中谷草转氨酶(GOT)、谷丙转氨酶(GPT)、碱性磷酸酶(ALP)、总胆红素(TBIL)含量,酶联免疫吸附试验法(ELISA)检测肝组织中谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)。实时PCR检测大鼠肝组织法尼醇X受体(FXR)、细胞色素7A1(CYP7A1)、过氧化物酶增殖物激活受体(PPAR α)表达,组织病理学观察大鼠肝脏病理学变化。结果:解剖观察肝重量、肝系数均无明显变化。与正常对照组比较,蒺藜粉高剂量组GOT显著升高(P<0.01),蒺藜水提物高剂量组GOT、GPT显著升高(P<0.05或P<0.01);蒺藜水提取物高剂量组GSH、MDA表达显著升高(P<0.05或P<0.01),中剂量组MDA表达显著升高(P<0.01),低剂量组SOD显著降低(P<0.05);蒺藜生药粉中、高剂量组CYP7A1表达显著升高(P<0.05或P<0.01);蒺藜水提物中剂量组CYP7A1表达显著升高(P<0.01),高剂量组PPAR α显著降低(P<0.01);组织病理学检查蒺藜粉中、高剂量组及蒺藜水提物各剂量组均可见肝细胞水肿、肝细胞脂肪变性,灶状炎细胞浸润,且蒺藜水提取物程度更深。结论:蒺藜水提物对肝脏的影响较为显著,且蒺藜肝毒性机制可能是抑制PPAR α的表达,使CYP7A1、MDA的表达过度所引起的。 |
English Summary: |
To investigate the hepatotoxic effects and mechanisms of Tribuli Fructus powder and aqueous extract.Methods:A total of 140 healthy SD rats(70 females and 70 males) were randomized into a normal control group,low-,medium-,and high-dose Tribuli Fructus powder groups,and low-,medium-,and high-dose Tribuli Fructus aqueous extract groups.Rats were administrated with Tribuli Fructus powder or aqueous extract by gavage for 1 month.The levels of glutamic oxaloacetic transaminase(GOT),glutamic pyruvic transaminase(GPT),alkaline phosphatase(ALP),and total bilirubin(TBIL) in the serum were measured.Enzyme-linked immunosorbent assay was employed to measure the levels of glutathione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD) in the liver.Real-time PCR was conducted to determine the expression of farnesoid X receptor(FXR),cytochrome P450 7A1(CYP7A1),and peroxisome proliferator-activated receptor α(PPARα) in the liver.The pathological changes of the rat liver were observed.Results:Neither the liver weight nor the liver index showed significant changes.Compared with the normal control group,high-dose Tribuli Fructus powder increased GOT(P<0.01),and high-dose Tribuli Fructus aqueous extract increased GOT and GPT(P<0.05 or P<0.01).High-dose Tribuli Fructus aqueous extract elevated the levels of GSH and MDA(P<0.05 or P<0.01),and the medium-dose aqueous extract only elevated the level of MDA(P<0.01).Low-dose Tribuli Fructus aqueous extract lowered the SOD level(P<0.05).The expression of CYP7A1 was up-regulated by medium and high doses of Tribuli Fructus powder(P<0.05 or P<0.01) and medium-dose Tribuli Fructus aqueous extract(P<0.01).The expression of PPARα was down-regulated by high-dose Tribuli Fructus aqueous extract(P<0.01).Histopathological examination showed hepatocyte edema,hepatocyte steatosis,and focal inflammatory cell infiltration in the medium and high dose groups of Tribuli Fructus powder and each dose group of Tribuli Fructus aqueous extract.Moreover,the pathological changes were severer in the Tribuli Fructus aqueous extract groups.Conclusion:The aqueous extract of Tribuli Fructus exerts obvious hepatotoxicity,which may be associated with the overexpression of CYP7A1 and MDA by the inhibition of PPARα expression. |
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