基于细胞铜死亡分析香砂六君子汤减少脾虚高脂血症大鼠肝脏组织脂质沉积的作用机制OA北大核心CSTPCD
Mechanism of Xiangsha Liujunzi decoction in reducing hepatic lipid deposition in rats with spleen-deficiency and hyperlipidemia based on cuproptosis
目的 从细胞铜死亡的角度分析中药香砂六君子汤减少脾虚高脂血症大鼠肝脏组织脂质沉积的作用机制.方法 将18只健康SD大鼠随机均分为正常组、脾虚高脂血症组、中药组.脾虚高脂血症组和中药组采用游泳力竭和高脂饲料喂养的复合方法造模,正常组仅给予普通饲料.造模12周后,中药组进行香砂六君子汤(11.34 g·kg-1)灌胃干预,正常组与脾虚高脂血症组给予同体积0.9%氯化钠溶液灌胃,灌胃干预4周后检测各组大鼠血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、肝脏脂积变化;PCR Array技术检测与铜死亡相关基因的表达.结果 与正常组比较,脾虚高脂血症组血清中TC、TG、LDL-C水平显著升高(P<0.01),HDL-C水平显著降低(P<0.01);脾虚高脂血症组大鼠肝脏脂质沉积明显.与脾虚高脂血症组比较,中药组TC、TG、LDL-C水平显著降低(P<0.01),HDL-C水平显著升高(P<0.01);中药组大鼠肝脏脂质沉积明显减少.PCR Array共检测出11个铜死亡相关基因.与正常组比较,脾虚高脂血症组肝脏铜死亡差异表达基因7个;与脾虚高脂血症组比较,中药组肝脏铜死亡差异表达基因6个;脾虚高脂血症组与中药组铜死亡共同差异表达基因5个.脾虚高脂血症组与正常组、中药组与脾虚高脂血症组差异表达均发生上调≥1倍或下调≤1倍的基因3个,2种比较方法结果取交集,共同的差异表达基因为Dld和Gls,这2个基因均能够调控线粒体铜死亡水平.qPCR验证结果显示,Dld基因表达与PCR芯片结果一致.结论 肝脏铜死亡相关基因(Dld、Gls)表达异常可能是血脂代谢异常的潜在机制,也可能是香砂六君子汤防治脾虚高脂血症的重要作用靶标.
Objective To investigate the mechanism of Xiangsha Liujunzi decoction in reducing hepatic lipid deposition in rats with spleen-deficiency and hyperlipidemia based on cuproptosis.Methods Eighteen healthy Sprague Dawley(SD)rats were randomly divided into normal,spleen-deficiency and hyperlipidemia,and traditional Chinese medicine(TCM)groups.Rats in the spleen-deficiency and hyperlipidemia group and TCM group were subjected to exhaustive swimming combined with a high-fat diet,while the normal group was fed an ordinary diet.After 12 weeks of modeling,rats in the TCM group were gavaged with Xiangsha Liujunzi decoction(11.34 g·kg-1),and the other two groups were gavaged with 0.9%sodium chloride solution in corresponding volume.After 4 weeks of intervention,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and liver lipid levels were measured.The mRNA expression levels related to cuproptosis were monitored using a PCR Array.Results Compared with levels in the normal group,the serum levels of TC,TG,and LDL-C in the spleen-deficiency and hyperlipidemia group were increased(P<0.01),while HDL-C was decreased(P<0.01).Compared with the spleen-deficiency and hyperlipidemia group,the TCM group showed decreased TC,TG,and LDL-C content(P<0.01),increased HDL-C content(P<0.01),and reduced lipid deposition in the liver.11 dif-ferentially expressed genes related to cuproptosis were detected using a PCR Array assay.Seven differentially expressed genes related to cuproptosis were found in the livers of the spleen-deficiency and hyperlipidemia group compared to those in the normal group;meanwhile,six differentially expressed genes were found in the TCM group compared with those in the spleen-deficiency and hyperlipidemia group.Five codifferentially expressed genes were identified among the abovementioned genes.Furthermore,three differentially expressed genes were found between the two paired comparison groups(≥1 fold or≤1 fold),and then Dldand Glswere screened out,which could reg-ulate mitochondrial cuproptosis.The expression levels of Dldand Glswere verified by qPCR,which were consistent with our PCR Array.Conclusion Abnormal expression of Dld and Gls related to cuproptosis in the liver may be a potential mechanism of abnormal lipid metabolism,and may be an important target of Xuanxiangsha Liujunzi decoction in the treatment of spleen-deficiency and hyperlipidemia.
刘慧慧;陈含希;冷雪
辽宁中医药大学中西医结合学院 生理与心理学教研室,沈阳 110847辽宁中医药大学中西医结合学院 生物化学与分子生物学教研室,沈阳 110847
中医学
香砂六君子汤脾虚高脂血症大鼠脂肪沉积细胞铜死亡
Xiangsha Liujunzi decoctionspleen-deficiencyhyperlipidemiaratlipid depositioncuprotosis
《中国医科大学学报》 2024 (004)
289-294 / 6
国家自然科学基金(82104552);辽宁省教育厅基本科研项目(JYTMS20231822)
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