健脾祛痰方影响TGF-β/PI3K/Akt通路减轻高脂血症大鼠内皮损伤  

Exploring Vascular Endothelial Protection Mechanism of Jianpi Qutan Recipe(健脾祛痰方)Based on TGF-β/PI3K/Akt Pathway

作　　者：韩晓萌 刘悦[2] 赵誉 于茂生 李子威 张艳[2] 杨关林[2] HAN Xiaomeng;LIU Yue;ZHAO Yu;YU Maosheng;LI Ziwei;ZHANG Yan;YANG Guanlin(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中华中医药学刊》2023年第8期196-200,I0032,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81703970);中国博士后科学基金面上项目(272830);辽宁省兴辽英才计划项目(XLYC2007057)。

摘　　要：目的 探讨健脾祛痰方基于TGF-β/PI3K/Akt信号通路对高脂血症大鼠的内皮保护作用。方法 使用60只SPF级雄性大鼠随机分为正常组、模型组、西药(阿托伐他汀)组和健脾化痰低、中、高剂量组。正常组给予基础饲料喂养,其余各组给予高脂饲料喂养,并活动受限,建立高脂血症大鼠模型。健脾祛痰各组给予不同剂量中药,西药组给予阿托伐他汀。12周后,苏木精-伊红染色(hematoxylin-eosin staining, HE染色)观察肝组织病理变化;酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测一氧化氮(Nitric oxide, NO)与内皮素-1(Endothelin-1,ET-1)水平;Western blot检测转化生长因子-β(Transforming growth factor-β,TGF-β)和单核细胞趋化蛋白-1(Monocyte chemoattractant protein-1,MCP-1)、磷脂酰肌醇-3激酶(Phosphatidylinositol 3-kinase, PI3K)、磷酸化磷脂酰肌醇-3激酶(phosphorylated phosphatidylinositol-3-kinase, p-PI3K)、蛋白激酶B(Protein kinase B,Akt)、磷酸化蛋白激酶(phosphorylated Akt, p-Akt)蛋白表达。结果 较正常组,模型组HE染色显示肝细胞肿胀和清晰的脂肪空泡,NO、TGF-β和MCP-1升高(P<0.01),ET-1、p-PI3K/PI3K、p-Akt/Akt下降(P<0.01)。与模型组相比,除健脾祛痰低剂量组MCP-1蛋白外(P>0.05),西药组和健脾祛痰组大鼠肿胀的肝细胞得到改善,脂肪空泡减少,NO、TGF-β和MCP-1降低(P<0.01),ET-1、p-PI3K/PI3K、p-Akt/Akt蛋白水平显著上升(P<0.01)。结论 健脾祛痰方可能通过影响TGF-β/PI3K/Akt通路改善高脂血症大鼠内皮损伤和炎症反应,发挥抗高脂作用。Objective To explore the protective effect of Jianpi Qutan Recipe(健脾祛痰方)on endothelium of hyperlipidemia rats based on transforming growth factor-β(TGF-β)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Sixty SPF male rats were randomly divided into normal group,model group,western medicine(atorvastatin)group,Jianpi Qutan Recipe low-dose,medium-dose and high-dose groups.The normal group was fed with basal diet,and the other groups were fed with high-fat diet.Jianpi Qutan Recipe groups were given different doses of Jianpi Qutan Recipe,and western medicine group was given atorvastatin.After 12 weeks,HE staining was used to observe the morphological changes of liver.The protein expressions of nitric oxide(NO)and endothelin-1(ET-1)were detected by enzyme linked immunosorbent assay(ELISA).Western blot was used to detect the protein expressions of PI3K,phosphorylated phosphatidylinositol-3-kinase(p-PI3K),Akt,phosphorylated Akt(p-Akt),TGF-βand monocyte chemoattractant protein-1(MCP-1).Results Compared with the normal group,HE staining showed liver cell swelling and clear fat vacuoles in the model group,the levels of NO,TGF-βand MCP-1 increased(P<0.01),while the levels of ET-1,p-PI3K/PI3K,p-Akt/Akt decreased(P<0.01).Compared with the model group,except for MCP-1 protein in the Jianpi Qutan Recipe low dose group(P<0.05),the swelling hepatocytes of rats in the western medicine group and Jianpi Qutan Recipe groups were improved.The fat vacuoles were reduced,the levels of NO,TGF-βand MCP-1 were decreased(P<0.01)and the levels of ET-1,p-PI3K/PI3K and p-Akt/Akt were increased significantly(P<0.01).Conclusion Jianpi Qutan Recipe may improve the endothelial injury and inflammatory response in hyperlipidemia rats by affecting the TGF-β/PI3K/Akt pathway,and plays an anti-lipid effect.

关 键 词：高脂血症 血管内皮损伤 TGF-β/PI3K/Akt信号通路 健脾祛痰方 

分 类 号：R285.5[医药卫生—中药学]