三七总皂苷调控PI3K/AKT信号通路预防糖尿病大血管病变的机制  

Mechanism of Panax Notoginseng Saponins Preventing Diabetic Macroangiopathy via PI3K/AKT Signaling Pathway

作　　者：杨春宁[1] 万多[1] 赵鹏 沈焕[1] 付鑫[1] YANG Chunning;WAN Duo;ZHAO Peng;SHEN Huan;FU Xin(Second Affiliated Hospital of Shenyang Medical College,Shenyang 110035,Liaoning,China)

机构地区：[1]沈阳医学院附属第二医院,辽宁沈阳110035

出　　处：《中华中医药学刊》2021年第2期118-121,I0024,I0025,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81874372)。

摘　　要：目的从PI3K/AKT信号通路研究三七总皂苷(panax notoginseng saponins,PNS)预防糖尿病大血管病变的机制。方法雄性SD大鼠分为对照组、模型组和治疗组,模型组和治疗组大鼠高脂饲料喂养6周后给予链脲佐菌素单次腹腔注射(30 mg·kg^(-1)体质量)建立2型糖尿病模型,成模后治疗组给予PNS灌胃干预(100mg·kg^(-1)体质量)。血糖仪检测大鼠空腹尾静脉血糖(FBG),ELISA法测定血清空腹胰岛素(FINS)和糖化血红蛋白(GHbA1c)水平,苏木素-伊红(HE)染色观察腹主动脉病理形态改变,荧光定量PCR检测腹主动脉标记物MMP2、MMP9、CD34、VEGF及PI3K、AKT mRNA相对表达,Western Blot法观察PI3K和AKT蛋白表达情况。结果模型组和治疗组大鼠在STZ注射造模后,FBG均显著高于对照组(P<0.01和P<0.01),两组间差异无统计学意义(P>0.05)。模型组和治疗组血清INS均显著高于对照组(P<0.01和P<0.01),治疗组INS显著低于模型组(P<0.05)。HE染色显示,与对照组比较,模型组动脉壁变薄,平滑肌细胞增多,排列紊乱,内膜不光滑;治疗组较模型组明显改善。模型组MMP2、MMP9表达较对照组显著上调(P<0.05和P<0.01),治疗组MMP9较模型组显著下调(P<0.01)。模型组CD34、VEGF表达较对照组显著上调(P<0.05和P<0.01),治疗组CD34较模型组显著下调(P<0.05)。模型组大鼠PI3K表达较对照组显著上调(P<0.05),治疗组PI3K表达较模型组显著下调(P<0.05)。模型组PI3K蛋白、p-AKT蛋白表达均显著高于对照组(P<0.01和P<0.01),治疗组PI3K、p-AKT均显著低于对照组(P<0.01和P<0.05),模型组p-AKT/AKT显著高于对照组(P<0.05),治疗组p-AKT/AKT较模型组有显著降低趋势,且与对照组差异无统计学意义。结论PNS可能通过下调PI3K/AKT信号通路预防糖尿病大血管病变。Objective To study the mechanism of Panax Notoginseng Saponins(PNS)preventing diabetic macroangiopathy via PI3 K/AKT signaling pathway.Methods Male SD rats were divided into control group,model group and treatment group.The model group and the treatment group were fed with a single intraperitoneal injection of streptozotocin(30 mg·kg^(-1)body weight)after 6-week high-fat diet to establish type 2 diabetes mellitus.In the treatment group,rats were given intragastric intervention of PNS(100 mg·kg^(-1)body weight)after the model was established.Blood glucose meter was used to detect fasting blood glucose(FBG)at caudal vein of rats.Levels of serum fasting insulin(FINS)and glycated hemoglobin(GHbA1 c)were measured by ELISA.Hematoxylin-eosin(HE)staining was used to observe pathological changes of abdominal aorta.The relative expressions of aortic angiogenesis markers MMP2,MMP9,CD34,VEGF,PI3 K and AKT were examined by qPCR.The expressions of PI3 K and AKT were observed by Western Blot.Results After STZ injection in the model group and treatment group,FBG was significantly higher than that in the control group(P<0.01 and P<0.01 respectively),and there was no significant difference between the two groups(P>0.05).The serum levels of FINS of the model group and treatment group were significantly higher than that of the control group(P<0.01 and P<0.01 respectively),and FINS of the treatment group was significantly lower than that of the model group(P<0.05).HE staining showed that in the model group,compared with those of the control group,the arterial wall became thinner,smooth muscle cells increased disarranged,and the intima was not smooth.The expressions of MMP2 and MMP9 in the model group were significantly increased compared with those of the control group(P<0.05 and P<0.01 respectively),while treatment group’s expression of MMP9 was significantly down-regulated compared with that of the model group(P<0.01).The expressions of CD34 and VEGF in the model group were significantly increased compared with those of the con

关 键 词：糖尿病血管病变 三七总皂苷 PI3K/AKT信号通路 胰岛素抵抗 高血糖 

分 类 号：R259.871[医药卫生—中西医结合]