摘要
目的研究黄芩苷对宫内发育迟缓(IUGR)胎鼠磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)通路的调控作用及对胰岛素抵抗的影响。方法取受孕成功CD-1小鼠25只,随机分成正常对照组、模型组和黄芩苷低(4 mg·kg^(-1))、中(8 mg·kg^(-1))、高(12 mg·kg^(-1))剂量组,每组5只。除正常对照组外,其余各组均采用10%低蛋白饲料喂养法建立IUGR模型,黄芩苷各剂量组给予相应剂量的黄芩苷溶液干预。各组孕鼠连续给药,于孕期第18日剖宫产取胎鼠,对应记为胎鼠正常对照组、模型组和黄芩苷低、中、高干预组,观察各组胎鼠死亡数量及成活胎鼠数量,计算各组胎鼠死亡率。各组随机取成活雄性胎鼠10只,分别称取体重、胰腺重量,酶联免疫吸附法检测胎鼠空腹胰岛素含量并计算胰岛素抵抗指数(HOMA-IR)和胰岛β细胞功能指数(HOMA-β);苏木精-伊红染色观察胎鼠胰腺组织形态;蛋白免疫印迹法检测胎鼠胰腺组织通路蛋白PI3K、AKT、磷酸化AKT(p-AKT)、胰岛素样生长因子1(IGF-1)、叉头框转录因子1(FoxO1)相对表达水平。结果与正常对照组相比,模型组胎鼠胰岛组织排列松散、轮廊模糊,胎鼠体重及体长、胰岛素水平、胰岛面积、HOMA-β以及胰腺组织PI3K、p-AKT/AKT、IGF-1、FoxO1蛋白相对表达水平降低(P <0.05),HOMA-IR升高(P <0.05);与模型组相比,黄芩苷低、中、高剂量组胎鼠胰岛排列紧密,体重及体长、胰岛素水平、胰岛面积、HOMA-β及胰腺组织PI3K、p-AKT/AKT、IGF-1、Fox O1蛋白相对表达水平呈剂量依赖性升高(P <0.05),HOMA-IR剂量依赖性降低(P <0.05)。结论黄芩苷可激活PI3K/AKT通路,促进IGF-1、FoxO1蛋白表达,改善IUGR胎鼠胰腺损伤及胰岛素抵抗。
AIM To investigate the regulation effect of baicalin on phosphatidylinositol 3-kinase/protein kinase B(PI3 K/AKT) pathway in fetal rats with intrauterine growth retardation(IUGR) and its influence on insulin resistance.METHODS A total of 25 pregnant CD-1 mice were randomly divided into normal control group, model group, and low(4 mg·kg^(-1)), medium(8 mg·kg^(-1)), high(12 mg·kg^(-1)) dose baicalin groups, with 5 mice in each group. Except the normal control group, the other groups were fed with 10% low protein diet to establish IUGR model, and baicalin groups were given corresponding doses of baicalin solution during pregnancy. The fetal mice of each group were taken by cesarean section on the 18 th day of pregnancy, and were recorded as normal control group, model group, and low, medium and high dose baicalin groups respectively. The number of dead or survival of fetal rats in each group were recorded, and the fetal mortality of each group was calculated. Ten surviving male fetal rats were randomly selected from each group, their body weight and pancreas weight were measured respectively, the fasting insulin content was detected by enzyme-linked immunosorbent assay,and insulin resistance index(HOMA-IR) and pancreatic β cell function index(HOMA-β) were calculated. Hematoxylineosin staining was used to observe the morphology of fetal pancreas. Western blot was used to detect the relative expression levels of PI3 K, AKT, phosphorylated AKT(p-AKT), insulin-like growth factor 1(IGF-1) and forkhead box transcription factor 1(FoxO1). RESULTS Compared with those in the normal control group, the islet tissues of fetal rats in the model group were loosely arranged and the contour was blurred, and the body weight, body length, insulin level, islet area, HOMA-β,and relative protein expression levels of PI3 K, p-AKT/AKT, IGF-1 and FoxO1 in pancreatic tissue were lower(P < 0.05),but HOMA-IR was higher(P < 0.05). Compared with those in the model group, the islets of fetal rats in the low, medium and high dose baicalin groups were arranged more closely, and the body weight, body length, insulin level, islet area, HOMA-β,and relative protein expression levels of PI3 K, p-AKT/AKT, IGF-1 and FoxO1 in pancreatic tissue increased in a dose dependent manner(P < 0.05), and HOMA-IR decreased in a dose dependent manner(P < 0.05). CONCLUSION Baicalin can activate PI3 K/AKT pathway, promote IGF-1 and FoxO1 protein expression, and improve pancreatic injury and insulin resistance in IUGR fetal rats.
作者
相萌
王春阳
张力
焦金雪
XIANG Meng;WANG Chun-yang;ZHANG Li;JIAO Jin-xue(Xi-an Medical University,Xi-an SHAANXI 710021,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2021年第10期718-723,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
陕西省教育厅专项科研计划项目(20JK0897)
西安医学院博士科研启动基金(2020D0C05)。
关键词
黄芩苷
宫内生长迟缓
胰岛素抗药性
胰岛素样生长因子
磷脂酰肌醇3激酶
蛋白激酶B
baicalin
intrauterine growth retardation
insulin resistance
insulin like growth factors
phosphatidylinositol 3-kinase
protein kinase B
