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基于TNF-α/MAPK/apoB-48通路研究首乌降脂汤对高脂血症金黄地鼠血脂的影响

Effect of Shouwu Jiangzhi decoction on hyperlipidemia Golden Syrian hamsters based on TNF-α/MAPK/apoB-48 pathway

  • 摘要: 为探究首乌降脂汤抑制小肠分泌apoB-48治疗高脂血症的机制,将20只金黄地鼠按体重随机分为空白组、模型组、非诺贝特治疗组和首乌降脂汤组。高脂饲料喂养4周建立高血脂模型,连续灌胃给药4 周后,微板法检测血脂指标高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)等的变化;酶联免疫法检测血清中肿瘤坏死因子-α(TNF-α)、载脂蛋白B-48(apoB-48)和游离脂肪酸(FFA)的水平;Western blot检测小肠组织中丝裂原活化蛋白激酶(MAPK)通路相关蛋白p38、ERK、JNK以及脂质代谢调节蛋白固醇原件蛋白(SREBP)、apoB-48的表达。实验结果显示首乌降脂汤可有效降低高血脂金黄地鼠血清中LDL-C、TG、FFA以及TNF-α和apoB-48的含量,显著下调小肠组织中JNK、p38、ERK、SREBP以及apoB-48的蛋白表达水平。上述结果提示首乌降脂汤可能通过抑制TNF-α /MAPK信号通路下调apoB-48的表达,发挥降血脂药效。

     

    Abstract: To investigate the mechanism of Shouwu Jiangzhi decoction in treatment of hyperlipidemia by suppress apoB-48 in small intestines, Golden Syrian hamsters were randomly devided into blank group, model group, fenobrate treatment group and Shouwu Jiangzhi decoction treatment group based on weight. The hyperlipidemia models of golden Syrian hamsters were induced by high fat diet(HFD)treatment for 4 weeks, then administered orally with drugs for 4 weeks. The serum indexes of HDL-C, LDL-C, TG and TC were determined by microplate methods, ELISA kits were used to evaluate the contents of serum TNF-α, apoB-48 and FFA. The protein expression levels of p38, ERK, JNK, SREBP, TNF-α and apoB-48 in small intestines were determined by Western blots. The results showed that Shouwu Jiangzhi decoction can effectively increase the serum HDL-C level and reduce the serum level of TG, LDL-C, TNF-α and apoB-48 in HFD-induced hamsters. Furthermore, Shouwu Jiangzhi decoction can significantly downregulate the protein expressions of p38, JNK, ERK, SREBP, TNF-α and apoB-48 in small intestines. Results above indicate that Shouwu Jiangzhi decoction may downregulate the protein expression of apoB-48 to treat hyperlipidemia via partially downregulating TNF-α/MAPK signal pathway.

     

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