芹菜素通过PI3K/Akt通路对妊娠期糖尿病大鼠胰岛素抵抗的作用

Effects of apigenin on insulin resistance and PI3K/Akt pathway in gestational diabetic rats

目的探究芹菜素对妊娠期糖尿病(GDM)大鼠胰岛素抵抗的影响,并初步探究可能的作用机制。方法于大鼠妊娠第5天,一次性尾iv 35 mg/kg链脲佐菌素混悬液制备GDM模型大鼠,随机分为模型组及芹菜素低、中、高剂量(10、20、40 mg/kg)组和二甲双胍(阳性对照,20 mg/kg),另设置正常妊娠大鼠为对照组,每组均12只。检测大鼠空腹血糖(FBG)、胰岛素(FINS)水平、胰岛素抵抗指数(HOMA-IR);全自动生化检测血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)水平;硫代巴比妥酸法检测血清丙二醛(MDA)水平;氮蓝四唑比色法检测血清超氧化物歧化酶(SOD)水平;HE染色观察胰岛组织病理形态学变化;半定量评分评估胰岛组织损伤情况;Western blotting法检测胰岛组织磷脂酰肌醇3激酶(PI3K)、p-PI3K、蛋白激酶B(Akt)、p-Akt蛋白表达。结果与对照组比较,模型组FBG、FINS、HOMA-IR显著升高,血清TC、TG、HDL-C水平显著升高,SOD水平显著降低,MDA水平显著升高,胰岛组织病理学评分显著升高,胰岛组织PI3K、Akt蛋白磷酸化水平显著降低(P<0.05);与模型组比较,芹菜素低、中、高剂量组与阳性对照组FBG、FINS、HOMA-IR显著降低,血清TC、TG、HDL-C水平显著降低,SOD水平显著升高,MDA水平显著降低,胰岛组织病理学评分显著降低,胰岛组织PI3K、Akt蛋白磷酸化水平显著升高(P<0.05)。结论芹菜素能够改善大鼠血糖、血脂,降低胰岛素抵抗、保护胰岛组织,其机制可能与激活PI3K/Akt信号通路有关。

Objective To investigate the effect of apigenin on insulin resistance in gestational diabetes mellitus(GDM)rats,and to explore the possible mechanism.Methods On the 5 th day of pregnancy,GDM model rats were prepared by tail iv 35 mg/kg streptozotocin suspension,GDM model rats were randomly divided into model group,apigenin low,medium and high dose(10,20 and 40 mg/kg)group and metformin group(positive control,20 mg/kg).Normal pregnant rats were set as control group,with 12 rats in each group.The levels of fasting blood glucose(FBG),insulin(FINS),insulin resistance index(HOMA-IR)and serum triglyceride(TG),total cholesterol(TC)and high density lipoprotein(HDL-C)were measured by automatic biochemical method,the level of malondialdehyde(MDA)was measured by thiobarbituric acid method,superoxide dismutase(SOD)was detected by azoblue tetrazole colorimetry,histopathological changes of islets were observed by HE staining,semi-quantitative scoring was used to evaluate islet tissue injury,and the expressions of phosphatidylinositol 3 kinase(PI3 K),p-PI3 K,protein kinase B(Akt)and p-Akt in islet tissues were detected by Western blotting.Results Compared with control group,FBG,FINS and HOMA-IR increased in GDM group,TC,TG and HDL-C increased,the level of SOD decreased,the level of MDA increased,the histopathological score of islets increased,and the phosphorylation levels of PI3 K and Akt proteins in islet tissue decreased(P<0.05).Compared with GDM group,FBG,FINS and HOMA-IR decreased in Apigenin low,medium and high dose groups and Metformin group,TC,TG and HDL-C decreased,the level of SOD increased,the level of MDA decreased,the histopathological score of islets decreased,and the phosphorylation levels of PI3 K and Akt proteins in islet tissue increased(P<0.05).Conclusions Apigenin can improve blood glucose and blood lipid,reduce insulin resistance and protect islet tissue.Its mechanism may be related to activation of PI3 K/Akt signal pathway.