基于蛋白质组学探讨丹参饮对高脂血症模型大鼠血脂异常的调节机制 点击下载
| 论文标题： | 基于蛋白质组学探讨丹参饮对高脂血症模型大鼠血脂异常的调节机制 |
| 英文标题： | |
| 中文摘要： | 目的 探讨丹参饮对高脂血症模型大鼠血脂异常的调节机制。方法实验大鼠分为空白组（n＝9，不造模）、模型组（n＝8，造模）和丹参饮组（n＝9，造模）。于高脂饲料喂养第9周开始，丹参饮组大鼠灌胃相应药液（3.6g/kg），空白组和模型组大鼠灌胃等体积生理盐水，每天1次，连续4周。给药4周后，检测各组大鼠血浆甘油三酯（TG）、胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平；观察大鼠肝脏组织病理形态学变化；采用TMT定量蛋白质组学分析筛选出样本间的差异蛋白；检测大鼠肝脏组织关键差异蛋白环氧化物水解酶2（EPHX2）、围脂滴蛋白2（PLIN2）、过氧化物酶体增殖物激活受体γ（PPARγ）、糖原合成酶激酶3β（GSK-3β）表达情况。结果与模型组比较，丹参饮组大鼠血浆TC、TG、LDL-C水平均显著降低（P＜0.05），HDL-C水平显著升高（P＜0.05）。模型组大鼠肝脏组织染色不均，肝板排列紊乱，肝血窦消失，部分细胞的细胞核固缩或消失，细胞质肿胀、融合，结缔组织增生，呈现弥散性空泡样脂肪滴改变；丹参饮组大鼠肝脏组织上述病理形态均有不同程度的改善。差异蛋白分析结果显示，模型组与空白组比较，差异蛋白总数为298个；丹参饮组与模型组比较，差异蛋白总数为139个。与模型组比较，丹参饮组大鼠肝脏组织中EPHX2、PLIN2蛋白表达水平均显著降低（P＜0.01），GSK-3β、PPARγ蛋白表达水平均显著升高（P＜0.01）。结论丹参饮对高脂血症模型大鼠血脂水平和肝脏病理形态学均有显著的改善作用，其调节机制可能与上调PPARγ、GSK-3β表达和下调EPHX2、PLIN2表达有关，涉及的信号通路可能包括PPARγ信号通路。 |
| 英文摘要： | OBJECTIVE To explore the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats. METHODS The experimental rats were divided into blank group （n＝9， no modeling）， model group （n＝8， modeling）， and Danshen decoction group （n＝9， modeling）. Starting from the 9th week of feeding with the high-fat diet， rats in the Danshen decoction group were given the corresponding medication solution （3.6 g/kg） intragastrically， while blank group and model group were given equal volume of normal saline， once a day， for 4 consecutive weeks. After 4 weeks of administration， the plasma levels of triglycerides （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured in each group of rats； the pathological and morphological changes of liver tissue were observed； the differential proteins between samples were screened out by TMT quantitative proteomic analysis； the expression levels of the key differentially expressed proteins in the liver， including epoxide hydrolase 2 （EPHX2）， perilipin 2 （PLIN2）， peroxisome proliferator activated receptor γ （PPAR γ） and glycogen synthase kinase-3β （GSK-3β）were detected. RESULTS Compared with the model group， the plasma levels of TC， TG and LDL-C in the Danshen decoction group were significantly reduced （P＜0.05）， while the level of HDL-C was significantly increased （P＜0.05）. The liver tissue of rats inmodel group showed uneven staining， disordered arrangement of liver plates， disappearance of liver sinusoids， nuclearcondensation or disappearance of some cells， swelling and fusion of cytoplasm， proliferation of connective tissue， and diffuse vacuolar-like fat droplet changes. The liver tissue of Danshen decoction group showed varying degrees of improvement in the above pathological and morphological. The results of differential protein analysis showed that the total number of differential proteins was 298 between the model group and the blank group； the total number of differential proteins was 139 between the model group and Danshen decoction group. Compared with the model group， the expression levels of EPHX2 and PLIN2 proteins in the liver tissue of rats in the Danshen decoction group were significantly reduced （P＜0.01）， while the expression levels of GSK-3β and PPARγ were significantly increased （P＜0.01）. CONCLUSIONS Danshen decoction has a significant improvement effect on the plasma lipid levels and the pathological and morphological of the liver tissue in hyperlipidemia model rats. Its regulatory mechanism may be related to the up-regulation of PPARγ and GSK-3β expression and down-regulation of EPHX2 and PLIN2 expression， and the signaling pathways involved may include PPAR-γ signal pathway. |
| 期刊： | 2024年第35卷第09期 |
| 作者： | 张玉昆；冯月男；卞敬琦；刘欣欣；肖洪彬；牛雯颖 |
| 英文作者： | ZHANG Yukun，FENG Yuenan，BIAN Jingqi，LIU Xinxin，XIAO Hongbin，NIU Wenying |
| 关键字： | 高脂血症；丹参饮；蛋白质组学；差异蛋白；过氧化物酶体增殖物激活受体γ；糖原合酶激酶3β |
| KEYWORDS： | hyperlipidemia； Danshen decoction； proteomics； differential protein； peroxisome proliferator activated receptor γ； |
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